Madridge Journal of Pharmaceutical Research

ISSN: 2638-1591

International Pharma Conference and Expo

May 2-4, 2018, Rome, Italy
Scientific Session Abstracts
DOI: 10.18689/2638-1591.a2.002

Orally Bioavailable Antimalarial 4(1H)-Quinolone and 4(1H)-Quinolone Prodrugs with Single-Dose Cures

Roman Manetsch1,2*, Fabian Brockmeyer1, Andrii Monastyrskyi3, Jordany R. Maignan3, Alexis N LaCrue4, Tina Mutka4 and Dennis E Kyle4,5

1Department of Chemistry and Chemical Biology, Northeastern University, USA
2Department of Pharmaceutical Sciences, Northeastern University, USA
3Department of Chemistry, University of South Florida, USA
4Department of Global Health, University of South Florida, USA
5Departments of Cellular Biology and Infectious Diseases, and Center for Tropical and Emerging Global Diseases, University of Georgia, USA

For approximately half a century, 4(1H)-quinolones such as endochin or ICI 56, 780 were known to be causal prophylactic and potent erythrocytic stage agents in avian but not in mammalian malaria models. Hit-to-lead optimization of endochin lead to 4(1H)-quinolones ELQ-300 and P4Q-391, which target the liver, the blood as well as the transmitting stages of the parasite (Sci. Transl. Med. 2013, 5, 177ra37). However, poor aqueous solubility severely limits absorption and oral bioavailability and therefore impedes preclinical development of this class of antimalarials Herein, we disclose a general prodrug approach that converts promising lead compounds, such as antimalarial 4(1H)-quinolones, into aminoalkoxycarbonyloxymethyl (amino AOCOM) ethers that display significantly improved aqueous solubility and enhanced oral bioavailability. The prodrug is autarkic, independent of biotransformations, and animal-independent as it activates via a pH-triggered intramolecular cyclization reaction. Amino AOCOM ether prodrugs of antimalarial 4(1H)-quinolones were shown to possess pharmacokinetic and efficacy profiles significantly improved relative to the corresponding parent compounds (> 50-fold improvement of Cmax and AUC). One of the most promising 3-aryl-4(1H)-quinolone preclinical candidates was further shown to provide single-dose cures in a rodent malaria model at an unprecedentedly low oral dose of 3 mg/kg, without the use of an advanced formulation technique.

Dr. Roman Manetsch received his PhD in Chemistry in 2002 from the University of Basel under the guidance of Wolf-Dietrich Woggon. He joined the group of K. Barry Sharpless at the Scripps Research Institute working on click chemistry. In 2005, he moved to the University of South Florida and established a research group focusing on medicinal chemistry. In 2014, Dr. Manetsch assumed a position of an Associate Professor at Northeastern University. His current research focuses on lead discovery and optimization using synthetic chemistry in close conjunction with mass spectrometry.

The Importance of Rapid Antigen Testing on Rational Antibiotic Use

Seyfullah Oktay Arslan*, Halil Kara and Deniz Uzun

Pharmacology Department, Ankara Yildirim Beyazit University, Turkey

Rapid antigen testing (RAT) has started to encourage the use of rational antibiotics in primary health care (family medicine department) in February 2017 in Turkey. The RAT is a practical test used to determine the presence of antigens of A group beta hemolytic streptococcus (AGS). This study aims to observe whether there is a difference in the rate of antibiotics prescription between years of 2016 and 2017, in which RAT was not used in the former and used in the later.

The most frequent bacterial agents of acute pharyngitis (AP) and tonsillopharyngitis (AT) are AGS. It is quite difficult to distinguish between viral or bacterial agents according to anamnesis, clinical and physical examination findings. Since the result of throat cultures requires 24-48 hours, various methods have been developed for fast determination the factors in AP and AT cases. The RAT test is one of them. The use of RAT is of great importance in reducing the use of irrational antibiotics and the cost of antibiotics.

A statistically significant difference was found in the antibiotic prescription of family physicians due to the use of RAT in the selected family medicine departments between the years of 2016 and 2017 (p<0.05). The RAT is a rapid and reliable method for the diagnosis of streptococcal AP and AT in outpatient. When RAT is positive, it indicates streptococcal AP and AT. However, negative detection of the testing does not remove it from the diagnosis. It is also observed that the use of RAT creates an important pharmacoeconomic awareness in physicians.

Keywords: Rapid Antigen Testing, Rational antibiotics use, Acute Pharyngitis, Acute tonsillopharyngitis, A group beta hemolytic streptococcus

Dr. Arslan is the head of pharmacology department in the Ankara Yildirim Beyazit University. His research interests focus on the experimental pathophysiology and inflammation of pulmonary and cardiovascular systems. He is the PhD supervisor for pharmacology and toxicology students.

Sulfasalazine/Dasatinib: A Novel Combined Therapy in Hepatocellular Carcinoma Cell Line

Marium Shamaa

Arab Academy for Science, Technology and Maritime Transport, Egypt

Hepatocellular carcinoma (HCC) is one of the most common human malignancies. Lack of efficient therapy for advanced HCC is a pressing problem worldwide. Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia (CML). The main targets of dasatinib, are BCRABL, SRC and GFR. NFκB is one of widely recognized positive regulator of cancer cell proliferation. It could be worthy to combine multikinase inhibitor with NFκB inhibitor for targeting of multiple signaling pathways involved in carcinogenesis. This study aimed to evaluate the potential anticarcinogenic effects of either dasatinib and/or sulfasalazine on HEPG2 cell line as a model of HCC. The current study was conducted on 4 groups.

For determination of the specific doses for the selected drugs MTT assay was done. While for laboratory investigations; cell lysates and nuclear extracts were subjected to ELISA and QRT-PCR. Both drugs have modulated RAF/ERK, BCR/ABL and NFκB pathways. Additionally, sulfasalazine confirmed its antiproliferative effects by lowering cyclin-D1, its apoptotic effect by improving the level of caspase-3, and its antiangiogenic effect by lowering VEGF level in a pattern similar to that of dasatinib. On the molecular level, dasatinib and sulfasalazine downregulated the gene expression level of c-MET. On almost all the parameters, the sulfasalazine effects were more superior when compared to that of dasatinib, while the combination regimen showed the best effects. The author present study showed for the first time the beneficial anticarcinogenic effects of dasatinib and sulfasalazine coadministration on HCC cells.

Dr. Marium Shamaa was Born in 1986, graduate of Elekbal Elkawmeya language school in Alexandria (class 2002), studied pharmaceutical science (2003–2007) at Alexandria University, Egypt. She received her master degree (2012) in Pharmacogenomics (IGSR, Alexandria University) and PhD degree (2016) in Biochemistry and Molecular Biology (IGSR, Alexandria University). She is studying the Clinical Pharmacotherapy Course at the active training company. She is now Lecturer of Biochemistry and Molecular Biology, college of Pharmacy, Arab Academy for Science, Technology and Maritime Transport, Alexandria, Egypt and simultaneously a member in the editorial board of the Universal Journal of Pharmaceutical Research. Her professional interests focus Pharmacotherapy, Pharmacogenetics, Oncology and Liver diseases.

Glitazones to Gliptins and Gliflozins: Quest for Cardio-Friendly Antidiabetics

Kiran Dubey

Department of pharmacology, Jamia Hamdard University, India

The well-characterized associations between type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) are twofold. First, CVD is the underlying cause of more than 60% deaths in diabetic patients. Second, the hyperglycaemia of T2DM, as measured by the percentage of glycosylated haemoglobin, is believed to increase the risk of coronary artery disease and myocardial infarction (MI). Given this relationship, physicians managing T2DM must remain aware of the cardiovascular effects of their therapeutic choices. Unfortunately, most oral antidiabetic therapies made available to date have not resulted in reduced incidences of MI, stroke or cardiovascular death in diabetic subjects. While metformin appears to be safe, it may lead to lethal lactic acid acidosis, especially in patients of recent MI or heart failure. An increased risk of all-cause mortality and cardiovascular related mortality has been associated with sulfonylureas and their combination with metformin. Meglitinides effects are similar to those of sulfonylureas, due to their analogous mechanism of action. Glitazones are unsafe in NYHA class III or IV due to weight gain and oedema. The cardiovascular safety outcome trials conducted with dipeptidyl peptidase-4 (DPP-4) inhibitors, saxagliptin and alogliptin showed an increase in hospitalization due to heart failure, while sitagliptin demonstrated no such effect. Evidence for cardiovascular benefits of glucagon-like peptide-1 (GLP-1) receptor agonists has been similarly heterogeneous, with liraglutide and semaglutide reducing the risk of composite cardiovascular outcomes, but lixisenatide having no reduction or increase in cardiovascular risk. The trial conducted with sodium-glucose co-transporter-2 (SGLT2) inhibitor, empagliflozin found it to be superior in reducing major cardiac events. However, there was a non-significant increase in silent MI with empagliflozin. While the FDA regulatory mandate to demonstrate the cardiovascular safety in order to approve new antidiabetic drugs, the quest for cardio friendly antidiabetics continues.

Dr. Kiran Dubey (M. Pharm, Ph.D. PGDMM) is currently associated with Jamia Hamdard as Assistant Professor in the Department of Pharmacology, School of Pharmaceutical Education and Research, New Delhi. She has also served in the Medical Information Department of Ranbaxy Laboratories, Systopic Laboratories, Dee Pharma Ltd and Skin Institute and School of Dermatology. Her areas of research include cardiovascular safety profile of NSAIDs, diabetes and related complications. She has guided twenty four post graduate students and three Ph.D. students in the field of Pharmacology and Pharmacy Practice, published articles and has been reviewer for International and National journals of repute.

Androgen Effect on the Muscular Expression of Neurotrophins; New Pharmacological Targets and Possible Modulators

Nasr Alrabadi1*, Haneen Sarairh1, Rasha Maraqa1, Mohammad Alqudah2, Ahmad Al-Dwairi2, Mahmood Al-Faqih2 and Othman Al-Shboul2

1Department of pharmacology, Jordan University of Science and Technology, Jordan
2Department of physiology and biochemistry, Jordan University of Science and Technology, Jordan

Androgens are natural and essential hormones in the development and function of body organs. As well, these hormones can be manufactured and administered to the body aiming to treat different pathological conditions. Anabolic steroids are forms of these manufactured androgens which are excessively used by body builders aiming to gain excessive muscle weight and strength. However, the abuse of anabolic steroids is associated with variety of catastrophic complications. This dose-dependent effect especially with the differences in the prevalence and prognosis of androgen related diseases between different sexes, can indicate to dose and sex-dependent paradoxical effects of these hormones.

Our group focus on studying the effect of wide range of androgen (sustanon) dosages/ concentrations on the differential expression of the main and well-known neurotrophins, so called; BDNF, NGF, NT3 and NT4/5. This expression is studied at the level of the heart, skeletal muscles and gastrointestinal wall (muscles) of either male/ female rats or chickens. Exploring this relationship will strengthen our understanding regarding the paradoxical effect of androgen usage among athletes. On the other hand, it may identify possible pharmacological targets and modulators for variety of pathological conditions related to what we call “androgen-neurotrophins axes”.

Dr. Nasr Alrabadi has completed his bachelor degree in medicine (2009) and received the Jordanian board for practicing medicine (2010). Dr Alrabadi completed his master degree in pharmacology (2012) and has been awarded his PhD in medicine and nanotechnology (2016) from Sydney University. Currently, he is assistant professor at the department of Pharmacology/ faculty of medicine, Jordan University of Science and technology (JUST) and a team leader for the molecular biology and analytical facility at the Nanotechnology institute/ JUST University. As a young researcher, he has 7 publications/abstracts.

More than Three Decades of Proton Pump Inhibitors

Abu-Freha Naim

Soroka University Medical Center and Ben-Gurion University, Israel

The lecture will include a review of this medications group, including the history and development of the different type of proton pump inhibitors, the differences between the different PPIs in term of pharmacodynamic and pharmacokinetic features.

Indications of treatments, efficacy of the drugs and the doses of the different PPIs and route of taking will be a part of the lecture.

The PPIs were considered as safe medications, however in the last decade the are more and more reports regarding different side effects, in the short term and long-term use. The talk will include a comprehensive review of the different reported side effects in the updated literature. Important side effects will be included in the talk, osteoporosis, fracture risk, gastrointestinal infections, pneumonia, iron deficiency anemia, vitamin B12 deficiency, hypomagnesemia and increasing risk of polyps and gastric cancer.

Another issue will be included in the lecture will be the updated recommendation regarding use of proton pump inhibitors during pregnancy and during breastfeeding. What about drug-drug interaction? and what about patients with chronic renal failure or liver cirrhosis? Should the dose be adjusted? These questions will be answered during the talk. The talk will be closed with the best practice advices regarding these drug group.

Dr. Naim Abu-Freha received his M.D. from the Tuebingen University, Germany at 2005 before becoming resident at internal medicine and then completed the gastroenterology residency at the Soroka Medical Center at 2014. He is a senior physician at the Institute for Gastroenterology and Hepatology, Soroka University Medical Center and lecturer at the faculty of Health science, Ben-Gurion University, Beer-Sheva, Israel. He deals with gastroenterology and hepatology in general, and especially with genetic syndrome of the colorectal cancer. He researched in different topics related to gastroenterology/Hepatology and different issues regarding the Bedouin Arab minority in southern Israel. He is one of the founders group of the Arab Medical Associations in the Negev (AMAN) and the first Chairman of the Associations since 2015.

Involvement of Inflammation in the Pathophysiology and Treatment of Mood Disorders

Abed N Azab* and Ahmad Nassar

Ben-Gurion University of the Negev, Israel

Introduction: Accumulating data suggests that inflammation plays a role in the pathogenesis and treatment of mood disorders. Consistently, classic anti-inflammatory drugs exerted beneficial effects in randomized clinical trials of mood disorders patients. Moreover, psychotropic drugs possess anti-inflammatory effects. However, despite these supporting findings, many contradicting results have also been reported.

Aims: (1) We investigated the effects of chronic treatment with psychotropic drugs on bacterial lipopolysaccharide (LPS)-induced inflammation in rats; (2) we tested the efficacy of mechanistically-different anti-inflammatory compounds in behavioral models in rats.

Materials and Methods: (1) Rats were treated with psychotropic drugs (carbamazepine, lithium, haloperidol, and imipramine) for 4 weeks through a daily intraperitoneal (ip) injection. On day 29, rats were injected with vehicle or LPS. At 2 hours later, rats were sacrificed, blood was collected and different brain regions were excised. Levels of inflammatory constituents in plasma and brain were examined by ELISA. (2) Rats were treated (ip) for 2 weeks with one of the following anti-inflammatory compounds: dexamethasone, a potent corticosteroid; nimesulide, a selective cyclooxygenase-2 inhibitor; montelukast, a leukotrienes receptors antagonist; pentoxifylline, a tumor necrosis factor-a inhibitor; and, JSH-23, a selective inhibitor of nuclear factor-k B. At the end of drug treatment, animals were subjected to a battery of behavioral tests.

Results: Psychotropic drugs treatment resulted in both anti- and pro-inflammatory effects. Some of the drugs prominently affected the levels of particular inflammatory mediators in the plasma and specific brain regions. Similarly, the various anti-inflammatory compounds differently affected the behavioral phenotypes of rats, showing both therapeutic and negative effects.

Conclusions: Our results add to the ambiguity regarding the role of anti-inflammation as a therapeutic strategy for mood disorders. It is important to elucidate the therapeutic potential of mediator/pathway-specific anti-inflammatory compounds in randomized clinical trials.

Dr. Azab completed his Ph.D. in pharmacology in the Department of Clinical Pharmacology in Ben-Gurion University of the Negev (Israel), focusing on the study of anti-inflammatory drugs. Subsequently, as a post-doctoral fellow in Wayne State University (Michigan), Dr. Azab investigated the mechanisms of mood-stabilizing drugs, focusing on the role of GSK-3 in inositol biosynthesis. Currently, Dr. Azab is an assistant professor in Ben-Gurion University of the Negev. Major research projects in his lab: 1) Studying the role of inflammation in the pathophysiology and treatment of mood disorders; 2) searching for novel therapeutic strategies for mood disorders.

Non-Invasive NaV Measurements using Molecular Imaging

Matthias Schoenberger

University of Leuven, Belgium

Voltage gated sodium channels constitute an integral component of electrical conduction in the heart and the nervous system. By depolarizing cardiomyocytes or neurons, they initiate action potentials that underlie the electro-mechanical coupling and neuronal firing. Changes in cardiac NaV function or expression levels can have severe consequences. For example, patients with loss-of-function or gain-of-function mutations in the SCN5A gene, which decodes cardiac NaV1.5, are at risk of suffering sudden cardiac death due to ventricular arrhythmias. However, it has not been possible to measure NaVs in vivo due to lacking molecular probes or techniques. To fill this gap and enhance our understanding of in vivo NaV function, we have developed the first positron emission tomography (PET) radiotracer for NaVs –radiocaine. In this talk, I will present the development and in vivo characterization of radiocaine and discuss steps towards future translational perspectives.

Dr. Matthias was born in Trier (Germany) and moved to Mainz University (Germany) for studying Biomedical Chemistry in 2004. During his study, he spend two research semesters at the Brookhaven National Laboratory (USA) and joined the laboratory of Joanna Fowler, pursuing research in radiochemical method development (11C) and in vivo positron emission tomography (PET) imaging. Matthias returned to Germany for his graduate studies in the International Max Planck Research School for Life Sciences (IMPRS-LS) in Munich with Dirk Trauner. His PhD-research was dedicated to organic chemistry, chemical biology and electrophysiology, yielding multiple first-in-classphotoswitchable ligands for ion channels and GPCRs. For his postdoctoral training, Matthias returned to the USA and the field of molecular imaging as a Marie-Slodowska-Curie fellow at Stanford University (Chemistry) and Harvard Medical School/MGH (Biomedical Imaging).
Matthiasʼ group in the pharmacy department performs KU interdisciplinary Leuven (Belgium research in Chemical Biology and Imaging with the goal of understanding ion channel dynamics in human disease.

Transforming Pharmacy Practice

Allan Mathews

Quest International University Perak, Malaysia

In ancient times, the pharmacist practiced side-by-side with the doctor in treating a patient giving the impression of equal responsibility bearing. The two professions were legally separated in the 13th century in Europe. The pharmacist retreated to the pharmacy and compounded medication according to the prescription received and dispensed to the patient carrying out instructions of the doctor. Compounding was the independent area of practice. With mass production of pharmaceutical dosage forms, the need for compounding became less and the pharmacist focused on dispensing of prescriptions expanding into prescription screening. Three main areas of practice evolved – community pharmacy, hospital/clinical pharmacy and industrial pharmacy. Community pharmacy evolved to a place where medicines are dispensed and became discount centers, shops selling items not related to healthcare and moving away from evidence‐based pharmacy. Countries vary in the extent of empowerment on the range of controlled medicines the pharmacist can deal without a prescription. Hospital/Clinical pharmacy evolved with the pharmacist being heavily involved in direct pharmaceutical care of patients while retaining custodianship of the medicine supply chain. Value creation and recognition continue to be a problem. The prescriber bears virtually the full responsibility. Prescribing by pharmacists has taken hold as well as expanded roles in administration of medicines and in medicine management. The challenge is how to develop independent areas of practice leading to responsibility bearing, value creation and recognition. Another challenge is to develop world‐wide commonality of practice. The focus of training of pharmacists should be to create full‐fledged practitioners rather than advisors.

Dr. Allan Mathews holds a B.Pharm (Hons) degree and post-graduate qualifications in Clinical Pharmacy, Operations Management, Sales Management and Marketing. He is a registered pharmacist in Malaysia as well as a life-member of the Malaysian Pharmaceutical Society. He also serves as a member of the Pharmacy Board of Malaysia. He has got 14 years of experience in Hospital/Clinical Pharmacy, 22 years in Industrial Pharmacy and 10 years in academia. He practices as a community pharmacist at the faculty-run community pharmacy in addition to his current role as the Dean of the Faculty of Pharmacy, Quest International University Perak, Malaysia.

Design and Synthesis of Ligands for G Protein-Coupled Receptor-1

Thet-Thet Htar1*, ShafiUllah Khan1, Kugernnes Nathan1, Nafees Ahemad1, Lay-HongChuah1,2 and Rakesh Naidu3

1School of Pharmacy, Monash University Malaysia, Malaysia
2Advanced Engineering Platform, Monash University Malaysia, Malaysia
3Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Malaysia

G protein-coupled estrogen receptor-1 (GPER-1, formerly known as GPR30) is a novel membrane receptor, which is noted to be able to mediate rapid estrogen signaling. It is widely expressed in cancer cell lines and primary tumour of breast, endometrium, ovaries, thyroid, lung, prostate, testicular germ cells and the brain. The high level expression of GPER-1 in breast cancer, ovarian cancer and endometrial cancer has shown association with poor survival. Due to its significant association with numerous physiological functions and breast cancers, it is emerging as a potential therapeutic target. In the search of GPER ligands, a variety of classical ER ligands have been noted to be able to interact with GPER-1 with differences in binding affinities. Some of the traditionally known ER antagonists have shown agonistic activity with GPER protein. As X-ray crystal structure GPER protein is not available, it has been a challenge in designing of GPER ligands. In this project, we studied the molecular structure requirement of GPER-1 ligands using homology model of GPER. We reported here approaches that have been used in homology modeling of GPER protein and synthesis of potential GPER ligands.

Dr. Htar is an academic lecturer and researcher in School of Pharmacy, Monash University Malaysia. She graduated with Bachelor of Pharmacy (Honours) in 1999 from the University of Wales, Cardiff where she successfully completed her PhD in 2004. Her current research interest is in the area of drug design and synthesis of small molecules with potential anti-cancer activity for the treatment of breast cancer. Her research interest has been extended to chemistry of natural products and synthesis of natural products based analogues. She has published a number of research and review articles in the area of synthesis and natural products.

Pharmacology of Endothelium and Vascular Smooth Muscle in Vascular System: The Comparison of Human Internal Mammary Artery (IMA) and Rat Aorta (RA)

Seyfullah Oktay Arslan

Pharmacology Department, Ankara Yildirim Beyazit University, Turkey

Vascular smooth muscle (VSM) and endothelium (ET) activities are the important determinants of vascular tone. This presentation evaluates the regulatory functions of VSM and ET in human internal mammary artery (IMA) and rat aorta (RA).

Potassium (K+) channels contribute to the regulation of the membrane potential in VSM cells. Membrane hyperpolarization due to efflux of K+results from the opening of K+channels and consequently vasodilation takes place. Various endogenous and exogenous substances, which form contraction and relaxation, alterthe vascular tone by interacting with their receptors in the VSM and ET.

The contraction and relaxation responses of the IMA and RA can be analyzed in vitro organ baths. Acetylcholine (ACh) produces endothelium-mediated relaxation while potassium chloride (KCl), phenylephrine (PE), and 5-hydroxytryptamine (5-HT) produce VSM-mediated contraction. ET-denuded vessels do not relax sufficiently by acetylcholine. ACh relaxes the ET-intact IMA and RA, it does not relax the ET-denuded IMA and RA. The KCl-induced contractions aremore stable and they last longer than those ofthe PE and 5-HT. However, the percentage of the PE and 5-HT induced contractionsare greater than that of KCl.

ET and VSM play an important role in the relaxation and contractions mechanisms of the IMA and RA. The physiological characteristics of IMA and RA in the formation of vascular tone are similar to each other. Different substances, which induce the relaxation and contraction in these vessels, also causevariedresponses.

Keywords: Endothelium, Vascular Smooth Muscle, Internal Mammary Artery, Rat Aorta

Dr. Arslan is the head of pharmacology Department in the Ankara Yildirim Beyazit University. His research interests focus on the experimental pathophysiology and inflammation of pulmonary and cardiovascular systems. He is the PhD supervisor for pharmacology and toxicology students.

Effects of Bulgarian Propolis on Cd34+ Cells In Vivo and on Two Cell Lines In Vitro

Lyudmil Peychev1, Elisaveta G Apostolova1, Milena N Draganova-Filipova2, Victoria S Sarafian2 and Zhivko Peychev3

1Department of Pharmacology and Drug Toxicology, Medical University of Plovdiv, Bulgaria
2Department of Medical Biology, Medical University of Plovdiv, Bulgaria
3Department of Medical informatics, Biostatistics and interactive education, Medical University of Plovdiv, Bulgaria

Purpose: To evaluate whether Bulgarian propolis augment the release of hematopoietic stem cells from bone marrow into the blood stream of rats and to analyze its effect on cell proliferation and surviving in vitro.

Methods: Twenty male Wistar rats were divided into two groups (n=10) and treated as follows:1-st group (Controls) – aqua destillata, p.o.; 2nd group-Bulgarian propolis in a dose 100 mg/kg bw, i.p. Two hours after single administration of the substances blood samples were analyzed by flowcytometry for CD34+ and white blood cells differential were performed using hematology analyzer.

Peripheral blood mononuclear cell (PBMC) and Mouse lymphoma cell line L5178Y were cultivated in 96 well plate in culture medium RPMI-1640 with 100 U/mL Penicillin and 100 mg/mL Streptomycin. 10% Fetal bovine serum was added to the L5178Y cell line. The cells were grown in an incubator at 37°C and 5% CO2 for 24 hours and were treated with increasing propolis concentrations - 0, 01; 0, 1; 1, 0 and 10 mg/L. To analyze the effect of the natural product on cell viability, a cytotoxic MTT-test was used.

Results: Propolis mobilized significant amount of hematopoietic stem cells in the blood stream versus controls. It also caused a significant increase in the number of leukocytes and lymphocytes in rats in comparison to controls. In human PBMC cells treated with propolis in concentrations 0, 01; 0, 1; 1, 0 and 10 mg/L the cell vitality was higher in comparison with the control cells. The percentage of living cell was increased from 106 to 135% with increasing of the propolis concentrations. In propolis treated tumor cells L5178Y the percentage of living cells decreased with increasing of propolis concentrations. The results of 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MMT) assay showed that concentration 0, 1 mg/L leads to 73% cell survival, 1, 0 mg/L to 69%, and the highest concentration-10 mg/L decreased the percentage of surviving cells to 40%.

Conclusion: Bulgarian propolis has no effect on the stem cells maturation but mobilize the rats stem cells in peripheral blood. In human PBMC the proliferative activity after treatment with propolis suppose the ability to influence cell differentiation. From the other side the cytotoxic effect of propolis on the tumor cell line determines its potential in anti-tumor therapy.

Keywords: CD34+ cells, cell lines, proliferation, rats, Bulgarian propolis.

Dr. Lyudmil Peychev, PhD, MHM, is Dean of the Faculty of Pharmacy at the Medical Medical University of Plovdiv, Bulgaria and Head of the Department of Pharmacology and Drug Toxicology. He is a specialist in Pharmacology, Clinical Pharmacology and Therapeutics, Master of Health Management. Professor L. Peychev is the author of scientific articles in the field of neuropharmacology, clinical pharmacology, phytotherapy and apitherapy. He is Head of research projects and author of inventions and trademarks. As a scientist he has won recognition by the academic community in Bulgaria and other countries.

Analysis of Isoniazid and Acetylisoniazid to Determine the Acetylation Rate of Melanesian Ethnicity from Papua

Yahdiana Harahap1*, Novi Yantih2, Wahono Sumaryono2 and Rianto Setiabudy3

1Department of Pharmacy, University of Indonesia, Indonesia
2Department of Pharmacy, University of Pancasila, Indonesia
3Department of Medicine, University of Indonesia, Indonesia

The major pathway of isoniazid (INH) metabolism is by acetylation to form acetylisoniazid (AcINH). The acetylation rate may differ depending on N-Acetyltransferase-2 (NAT-2) activity. The aim of this research was to determine INH acetylation rate on Melanesia ethnicity from Papua, Indonesia. The rate of acetylated INH was determined based on the ratio of AcINH and INH levels in human plasma which was analysed using HPLC. The chromatographic separation was conducted using Reliant® C18 column (250x4.6mm)with temperature of 30°C, a 20 mM hexane sulphonic acid pH 2.47-methanol (65:35) as mobile phase with a flow rate of 1 mL/mins, detected at 265 nm, and vitamin B6 as an internal standard. The participants in this study were healthy subjects from Papua and 102 subjects completed the study. The blood was collected at pre-dose and 3 hours after administration of 300mg INH. The results showed that 70.59% of subjects were slow acetylators, it means that the Melanesia ethnic from Papua need more dosages to achieve the therapeutic concentration of INH.

Dr. Yahdiana Harahap is a Professor in the field of Pharmaceutical Chemistry especially Bioanaysis related to bioequivalence study and DNA Adduct. She received her Master Degree in 1994 and Doctoral degree in 2003 from Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Institute Teknologi Bandung. She has been The Head of Bioavailability-Bioequivalence Laboratory Faculty of Pharmacy Universitas Indonesia since 2008. She has generated more than 80 scientific works published in international and national journals, thus presented them in national and international conferences.

Kinetic Target-Guided Synthesis: A Ms-Based Fragment Evolution Platform

Roman Manetsch1,2*, Prakash Parvatkar1, Katya P Nacheva3, Sameer S Kulkarni3, Niranjan K Namelikonda3, David L Flanigan3 and Andrii Monastyrskyi3

1Department of Chemistry and Chemical Biology, Northeastern University, USA
2Department of Pharmaceutical Sciences, Northeastern University, USA
3Department of Chemistry, University of South Florida, USA

The Manetsch laboratory focuses on the development and implementation of LC/MS-based lead discovery and optimization platforms. Herein, the development of kinetic Target-Guided Synthesis (TGS) and its implementation for the identification of small molecules modulating protein-protein interactions will be presented. In kinetic Target-Guided Synthesis (TGS), the biological target is actively engaged in the irreversible assembly of its own inhibitory bidentate ligand from a pool of smaller reactive fragments. The screening method can be as simple as determining whether or not the inhibitory product has been formed in a given test mixture. To date, kinetic TGS has exclusively been applied to enzymatic targets and these TGS applications have been successful because of a unique combination of (a) the slow nature of the chemical reaction combining the two fragments into a single molecule and (b) the use of reactive fragments showing moderate to high affinity towards binding pockets of the enzyme. Compared to kinetic TGS screening of enzymes, however, the discovery of inhibitory compounds against “undruggable” targets is more challenging and thus requires major modifications over the existing kinetic TGS approaches. The Manetsch laboratory demonstrated that the sulfo-click reaction, an amidation reaction between thio acids and sulfonyl azides, is suitable for a kinetic TGS approach targeting the proteins of the Bcl-2 family. Furthermore, the use of a triple quadrupole mass analyzer improved the data quality and increased the throughput by approximately 200-fold rendering the platform industrial robustness.

Dr. Roman Manetsch received his PhD in Chemistry in 2002 from the University of Basel under the guidance of Wolf-Dietrich Woggon. He joined the group of K. Barry Sharpless at the Scripps Research Institute working on click chemistry. In 2005, he moved to the University of South Florida and established a research group focusing on medicinal chemistry. In 2014, Dr. Manetsch assumed a position of an Associate Professor at Northeastern University. His current research focuses on lead discovery and optimization using synthetic chemistry in close conjunction with mass spectrometry.

Scaffolds Based on Electrospun Nanofibers for Wound Healing

Giuseppina Sandri*, Silvia Rossi, Maria Cristina Bonferoni and Franca Ferrari

*Department of Drug Sciences, University of Pavia, Italy

Centre for Health Technologies, University of Pavia, Italy Electrospinning is a one-step and simple method to manufacture membranes based on (nano) fibers having diameters ranging from 20 nm up to 1 mm and more. Scaffolds based on nanofibrous membranes could allow protecting chronic skin lesion them from microbial contamination and optimal wound hydration and gas exchanges, crucial for healing, and should be a substrate able to induce cell adhesion and growth, speeding up the healing process.

Given this premises the aim was the development of electrospun nanofibers based membranes as scaffolds to enhance cutaneous wound healing of chronic lesions and burns.

The nanofibers were prepared starting from aqueous polymeric solutions to obtain insoluble membranes in aqueous fluids able to act as a support for cell growth, migration and proliferation.

Nanofibers were loaded with either silver nanoparticles ornorfloxacin, as antimicrobial agents.

Chitosan and a glycosaminoglycan (hyaluronic acid or chondroitin sulfate)wereselected as biomaterials. The developed scaffolds based on biopolymers are characterized by flexible area and shape with suitable elasticity and mechanical properties, are able to maintain optimal hydration and to absorb excess of fluids, to form barrier against microbial contaminations and to release antimicrobial agents. The presence of antimicrobials agents do not impair cell adhesion (fibroblasts and endothelial cells) and proliferation in an in vitro models.

The in vivo evaluation in murine burn model suggests that scaffolds are effective to enhance wound closure without signs of inflammation and adverse effects.

Dr. Giuseppina Sandri (PhD in Chemistry and Pharmaceutical Technology) is Associate Professor at Drug Science Department (Faculty of Pharmacy) at University of Pavia, Italy.
Current research concerns the development medical devicesand antimicrobials based formulations based on electrospun nanofibers for skin and hearth regeneration. Her research activities were awarded with national and international awards and were founded with public and private grants. She takes part in joint research projects with Universities andpharmaceutical companies. She serves as reviewer for several scientific journals.
Total number of referred publications:86 contributions published on scientific journals, 12 book chapters, 3 patents;Hindex:25 (Scopus).

Development and Efficacy Evaluation of Topical Preparations for Nail Disorders

Paola Perugini*, Marcello Bracchi and Priscilla Capra

Department of Drug Sciences, University of Pavia, Italy

This presentation proposes an overview of the development and testing of effective treatment for nail disorders, in particular onychodystrophy that is an alteration of the tropism of the nail, due to systemic and local causes. Topical treatment avoids adverse effects associated with systemic therapy. However, the effectiveness of topical therapies is limited because of the poor permeability of the lamina to the therapeutic agents applied. In fact, it must be borne in mind that the nail is basically a tortuous twist of crystalline and amorphous fibrous proteins in which only small molecules pass through.

In recent years the research has mainly focused on improving transdermal permeability by chemical treatments, penetration enhancers, mechanical and physical methods. For this purpose, several “ex vivo” methods have been studied, including the use of bovine membranes as a human nail substitute for penetration studies.

The aim of recent works was to evaluate whether and to what extent such in vitro tests can correctly predict the in vivo fate of nail lacquers.

In the application of pharmaceutical lacquers used to treat nail alterations and fungal infections, the location of the film on the nail lamina and the transungueal passage of the active substance are the key factors.

Hence the importance of developing topical products with appropriate formulation both in terms of medical treatment and associated cosmetic treatment. In fact, the constant use of an inappropriate cosmetic formulation can severely compromise the effectiveness of medical treatment.

Dr. Paola Perugini, graduated in Pharmaceutical Technology and Chemistry (CTF) and in Pharmacy, earned her PhD in Pharmaceutical Technology and Chemistry in 1998. Now she is an associate Professor at the University of Pavia in which she teaches in Pharmacy and in CTF degree courses. Furthermore she is the Coordination of the Master Degree in “Cosmetological Sciences” at the University of Pavia from 2009-2010.
The main research activities of Perugini concerning pharmaceutical and cosmetic technology. The scientific work of Dr. Perugini has resulted in over 60 publications, 2 patents, more than 100 communications on topics of technology pharmaceutical and cosmetics.

Hepatoprotective Properties of the Salt-Like Derivatives of the Drug Xymedon with Biogenic Acids

Vyshtakalyuk A B1, Parfenov A A1, Gumarova L F1, Kondrashina D A1, Galyametdinova I V1, Semenov V E1, Nazarov N G1,2, Zobov V V1,2, Hasanshina L R2, Belyaev G P2 and Diabankana R G K2

1Subdivision of the Federal State Budgetary Institution of Science “Kazan Scientific Center of Russian Academy of Sciences” Russia
2Kazan Federal University, Russia

The objective of this work was an evaluation of hepatoprotective activity of derivatives of drug Xymedon (1-(ß-oxyethyl)-4.6-dimethyl-1.2-dihydro-2-oxopirimidon) (I) with biogenic acids succinic, L-ascorbic, para-aminobenzoic, nicotinic, L-2-amino-4-(metyltio)butane (L-methionine) (II-VI respectively). Formerly, we have shown that (I) possesses ability to stimulate liver recovery after toxic damage by CCl4 [1]. New data are on derivatives (III, IV) that have a better specific capability if compared with (I) to stimulate spinal marrow recovery after trauma [2], improve bodyʼs adaptation under physical stress [3,4], as well as demonstrate hepatoprotective properties [5-7]. We observed the most pronounced hepatoprotective properties of derivative (III) [6], because the compound results to minimum liver injury of steatosis and necrosisand normalize of biochemical parameters in rats with toxic hepatitis induced by CCl4. It was revealed the effect of the compound (III) on the antioxidative system and on the cytokines level in liver during toxic influence of CCl4. The number of pathological changed hepatocytes as fatty, balloon and hydropic dystrophy were decreased if injected with (III). The derivative (III) is more effective in comparison with other derivatives of Xymedon as well as with Xymedon, L-ascorbic acid, their mix and their co-administration and the drug Thiotriazolinum.

The research was financed by Russian Science Foundation grant number 14-50-00014.

Dr. Vyshtakalyuk A B is a senior researcher, Doctor of biology in the International research and innovation center of neurochemistry and pharmacology of A.E. Arbuzov Institute of Organic and Physical Chemistry - Subdivision of the Federal State Budgetary Institution of Science “Kazan Scientific Center of Russian Academy of Sciences”, Kazan, Russia. She graduated from Kazan State University in 1994, got PhD in Physiology of Human and Animals in 2000 and degree of Doctor in biology in 2015. She is head of the small team that studies hepatoprotective, anti-anemic and anti-inflammatory properties of new compounds. Her science interest is in the area of pharmacology, immunology, hematology and metabolism.

In Vitro Permeation and Pharmacokinetic Evaluations of a Novel Transdermal Formulation of CZ48, Lactone-Stabilized Camptothecin-C20-Propionate, for Cancer Treatment

Yousif Rojeab

Department of Pharmaceutical and Biomedical Sciences, Ohio Northern University, USA

Camptothecin (CPT) is a promising anti-cancer agent with high efficacy against a variety of solid tumors. The lactone ring of CPT is essential for the anti-tumor activity but is unstable in vivo. A pro-drug of CPT, CZ48, has been developed where CZ48 is enzymatically hydrolyzed in vivo to active CPT. For its anti-cancer activity, CPT levels need to be sustained and maintained over a period of time, which means the requirement for a continuous delivery of CZ48. It has been demonstrated that I.V. bolus injection of CZ48 provided higher concentrations of the active CPT compared to direct dosing of CPT at the same dosing level in Sprague-Dawley rats. Also, it was shown that CZ48 dosing resulted in sustained plasma levels of CPT for five hours in this animal model. Therefore, if we extrapolate these observations to man, we would expect to see this pattern of sustained CPT levels upon administration of the pro-drug, CZ48. This means delivery of CZ48 can achieve a continuous, therapeutically relevant drug concentration of CPT for anti-neoplastic indications. Transdermal delivery satisfies the requirement for continuous CZ48 delivery since it allows for predictable and controlled drug permeation through the skin. A promising approach to deliver drug molecules transdermally is through a microemulsion formulation. Our in vitro permeation data through excised rat skin as well as in vivo data upon topical application in Swiss-nude micedemonstrate the feasibility of achieving sustained plasma levels of CPT, required for anti-tumor activity, upon transdermal application of the pro-drug, CZ48.

Dr. Rojeab is currently an Associate Professor of Pharmaceutics at the Raabe College of Pharmacy, Ohio Northern University inAda, OH, USA. He received his B.Sc. in Pharmacy in 1999 and Ph.D. in 2007 in Pharmaceutics from University of Houston, TX. He is also a licensed pharmacists in the states of OH, MI & TX. Current research in Dr. Rojeabʼs lab involves two main areas. First is the physicochemical characterization, preformulation, formulation and delivery of anti-cancer agents. The second research area involves bioavailability/bioequivalence evaluations of novel and conventional orally administered solid dosage forms in man.

Nanotechnology-based Drug Delivery to Skin

Fiorenza Rancan1*, Jana Jurisch1, Annika Vogt1, Michael Giulbudagian2, Marcelo Calderón2, Marco Contardi3, Ilker Beyer3 and Christoph Schaudinn4

1Charité - University Medicine Berlin, Germany
2Free University of Berlin, Germany
3Italian Institute of Technology, Italy
4Robert Koch Institut, Germany

Nanotechnology-based carrier systems allow improving drug permeation, spreading within the tissue, retention, and even targeted and stimuli-responsive drug delivery. In skin inflammatory diseases, immune cells are the main key actors and thus the target of therapeutic treatments. Targeting of certain cell populations like dendritic cells may be achieved by means of biocompatible nanocarriers that can translocate to the skin viable layers. Thermoresponsive polyglycerol-based nanogels (tNGs) have been shown to penetrate very efficiently the outermost skin barrier and to be valuable tools for delivery of drugs to skin. In order to develop new types of formulations for anti-inflammatory dermatotherapy, tacrolimus, a high molecular weight, poorly skin penetrating drug, was loaded on thermoresponsive nanogels. Compared toa commercial formulation (Protopic 0.1%), the water-based nanogel formulation had comparable effects on an inflammatory skin model. On the other side, in the case of skin and wound infections, high local concentrations of the active material are necessary to eradicate the invading microorganism and avoid the development of resistances. At this purpose, we used PVP-based foils and nanofibers to deliver antimicrobial drugs in an infected wound model based on ex vivo human skin. Different delivery profiles were achieved depending on the used drug delivery system. Nanocarriers efficiently delivered drugs across the skin barrier with significant inhibitory effects on immune cells where as nanofibers and foils provided a sustained drug concentration within the skin tissue as well as very efficient antimicrobial effects. We conclude that nanotechnology-based drug delivery systems offer attractive alternatives to conventional drug formulations.

Dr. Fiorenza Rancan is private lecturer and associated scientist in the Clinical Research Center for Hair and Skin Science at the Dermatology Department of the Charité – Universitätsmedizin Berlin. She earned a doctorate in Chemistryfrom the Humboldt University of Berlin and adegree in Pharmaceutical Chemistry and Technology from the University of Padua, Italy. Dr. Rancan expertise lays ondermal and transdermal drug delivery. Her main research topics are the development of new antimicrobial treatments using skin models for infected wounds, antigen and adjuvant delivery for transcutaneous vaccination, stimuli-responsive nanocarriers for the treatment of skin inflammatory conditions.

Activation of the AIM2 Inflammasome in Peripheral Blood Mononuclear Cells (Pbmcs) from Idiopathic Pulmonary Fibrosis Patients Leads to the Release of Pro-Fibrotic Mediators

Rosalinda Sorrentino1*, Michela Terlizzi1, Rita P Aquino1, Aldo Pinto1, Chiara Colarusso1,2, Antonio Molino3, Pasquale Imitazione3, Pasquale Somma4, Chantal Donovan5 and Philip M Hansbro5

1Department of Pharmacy, Immune Pharma s.r.l., University of Salerno, Italy
2Department of Pharmacy, University of Salerno, Italy
3Department of Respiratory Medicine, University of Naples Federico II
4Department of Anatomy and Pathology, Naples, Italy
5Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Australia

Idiopathic pulmonary fibrosis (IPF) is a chronic fibro-proliferative disease characterized by poor prognosis, with a mean survival of ~2–3 years after definite diagnosis. The cause of IPF is still unknown but it is a heterogeneous condition in which the aberrant deposition of extracellular matrix leads to extensive lung remodeling. This remodeling is a consequence of inflammatory responses, but the mechanisms involved are poorly understood. In this study, we first analyzed a bleomycin-induced mouse model, which showed that higher expression of IL-1β, but not IL-18, was correlated to pulmonary cell infiltration and fibrosis. Then, we found that peripheral blood mononuclear cells (PBMCs) from IPF patients released higher levels of IL-1α and IL-18 in a NLRP3- and calpainin-dependent manner after LPS±ATP. Instead, the activation of the AIM2 inflammasome induced the release of IL-1α in a caspase-1/-8 independent manner; whereas IL-18 release was caspase-1-dependent. These effects correlated with the release of the pro-fibrotic TGF-β, which was induced by AIM2 activation in a caspase-1- and TLR4-independent manner, but dependent on IL-1α. In this context, the activation of AIM2 induced the release of caspase-4 from IPF-derived PBMCs, which correlated with the mRNA levels of this caspase that was higher in IPF than in healthy PBMCs.

In conclusion, our findings identify a novel molecular mechanism whereby the activation of AIM2 could lead to the activation of the non-canonical inflammasome (caspase-4-dependent), that induces the release of IL-1α responsible for the release of TGF-β from PBMCs of IPF patients.

Dr. Rosalinda Sorrentino, PhD, is actually a Tenure Track Research Scientist at the University of Salerno. During her PhD training, Dr. Sorrentino joined Prof. Jane Mitchellʼs laboratory at Imperial College-NHLI (UK) as a visiting scientist. In 2007 Dr. Sorrentino obtained a PostDoctoral Position at Cedars Sinai Medical Center, USA. In 2008 she moved to Italy to establish her own research project to understand how chronic inflammation in the lung favors malignancy.

Penetration of Microparticles across Mucus Barriers: A Colloidal Probe Microscopic Approach

Seunghwan Lee* and Nikolaos Nikogeorgos

Department of Mechanical Engineering, Technical University of Denmark, Denmark

Mucus represents “first defense line” of all mucosal surfaces, such as gastrointestinal, cervical, ocular, respiratory lines against chemical, enzymatic, microbial, and mechanical insult. While pathogenic colonization by microbes starts from adhesion on mucus surface, they have to overcome the mechanical integrity of mucus gels in order to reach the apical surface of epithelial cells. Ironically, this defensive behavior of mucus gels acts as physical barrier when it is needed to deliver drug molecules or functional foods to target cells or tissues. Mucoadhesive polymers have been proposed as one of potent ways to enable the traverse of drugloaded particles through mucus gel layers based on strong entanglement with mucin network. Nevertheless, it is often not sufficient to reach ultimate goal, i.e. delivery of drugs to target cells, due to relatively short turnover time and frequent clearance of mucus gels. It is thus necessary to develop more effective means to engineer particles that can efficiently “penetrate through” the barrier for this purpose. In this study, we have employed atomic force microscopy (AFM) as an experimental approach/model to characterize the nanomechanical properties of mucus gels and the interaction with microbes and drug/function nutrients. Mucus was acquired by scraping from a freshly slaughtered pigʼs stomach and intestine, and was further cleaned according to a standard procedure. Polyethylene (PE) or silica (SiOx) colloidal particles were attached to AFM probes, representing model microbes or drug molecules interacting with mucus layers. Youngʼs moduli of both mucus samples were determined to be in kPa range. In-depth discussion on the mechanical properties of pig intestine mucus, the influence of size and surface chemistry of the colloidal probe on the compression/penetration, as well as the force/energy required for a micro-sized particle to overcome and penetrate through the mucus layers will be provided.

Dr. Seunghwan Lee completed PhD in physical chemistry in 2000(University of Houston), then worked in the field of biotribology and biomimetic lubrication at ETHZ, Switzerland until 2008. Since 2009, he has been leading a research group focusing on biotribology of mucin, mucus, orthopaedic implants, and antifouling properties at the Department of Mechanical Engineering, DTU, Denmark.

Organolithium Chemistry using Flow Microreactors

Aiichiro Nagaki

Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Japan

Many successful applications reported in the literature speak well for the power of the flow-microreactor method in chemical synthesis. The reaction time in a flow microreactor is defined as the residence time between a reagent inlet and the quencher inlet, which can be controlled precisely and reduced to millisecond order by adjusting the length between these positions and the flow speed. Such a feature of flow microreactors enables the use of short-lived highly reactive intermediates for synthesis. Various intermediates can be rapidly generated and transferred to another location in the flow system for use in subsequent reactions before they decompose. Protecting-group-free synthesis has received significant recent research interest in the context of ideal synthesis they decompose. Protecting-group-free synthesis has received significant recent research interest in the context of ideal synthesis and green sustainable chemistry. In general, organolithium species react with electrophilic functional groups very rapidly, and therefore such functional groups should be protected before an organolithium reaction, if they are not involved in the desired transformation. If organolithium chemistry could be free from such a limitation, its power would be greatly enhanced. A flow microreactor enables such protecting-group-free organolithium reactions by choosing the appropriate residence time and the reaction temperature. Organolithium species bearing alkoxycarbonyl, nitro, ketone and aldehyde carbonyl groups can be generated by lithiation of the corresponding organic halides and reacted with various electrophiles using a flow microreactor system. In this presentation, we report that a flow microreactor system enables the generation of various unstable organolithium compounds.

Dr. Aiichiro Nagaki has received his Ph.D. in 2005 from Kyoto University under the supervision of Professor Jun-ichi Yoshida. He worked with Professor Hiroaki Suga, Tokyo University from 2005 as a postdoctoral fellow. In 2006, he became an assistant professor of Kyoto University. In the year 2013 he promoted to Junior Associate Professor. His current research interests are organic synthesis, polymer synthesis, and microreactor synthesis. Awards: Takeda Pharmaceutical Co., Ltd. Award in Synthetic Organic Chemistry, Japan (2012), Incentive Award in Synthetic Organic Chemistry, Japan (2012), and Young Innovator Award on Chemistry and Micro-Nano Systems (2013).

New Discovery of Treatment of Complicated Hemorrhoids without Surgery

Ahmed M A Masaad*

Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, Taif University, Saudi Arabia

Hemorrhoids, also called piles, are vascular structures in the anal canal. In their normal state, they are cushions that help with stool control. They become a disease when swollen or inflamed; the unqualifiedly term “hemorrhoid” is often used to refer to the disease. The signs and symptoms of hemorrhoids depend on the type present. Internal hemorrhoids are usually present with painless, bright red rectal bleeding when defecating. External hemorrhoids often result in pain and swelling in the area of the anus. If bleeding occurs it is usually darker. The new treatment is mainly depend on mechanism of contract the connective tissue surrounding the venous around anus by effervescent tannin base with strong anti-bacterial, antifungal and anti-viral effect of formula. The safety of drugs was tested in rabbits, rats first and then the experiment was done in hundreds of patient under license of ethics committee of Taif University. The percentage of cure conducted was 99%, this success leads to relive of pain over millions of patients around the world and minimize the risk of surgery treatment and cost beside quick relive of disease in two to three weeks with no chance of relapse of disease again.

Dr. Ahmed M. A. Massad is concern with discovery of new drugs and innovation in many new drugs and drug delivery system. Dr. Ahmed has memberships in many scientific societies and editor of PSC journal. He published more than twenty scientific researches in many sides of pharmacy, he discovered new treatment of cancer of colon and skin, possess innovative certificates in drugs delivery system and new drugs which are published in scientific journal.

Antibacterial Activity of Ethanolic Extract and Nanoparticles Ethanolic Extract of Javanese Turmeric Rhizome (Curcuma xanthorrhiza Roxb.)

Shirly Kumala*, Benny, Yunahara and Deni Rahmat

University of Pancasila, Indonesia

The aim of this study was to compare the antibacterial activity of 96% (v/v) ethanolic extract of Javanese turmeric (Curcuma xanthorrhiza Roxb.) and nanoparticle containing the extract against4 pathogenic bacterias. The method to formulate the nanoparticles extract was ionic gelation using chitosan and sodium tripolyphosphate. The resulting nanoparticles were evaluated for particle size, zeta potential and morphology. The nanoparticle showed a good result, as the particle size was 53.25 nm and polydispersity index was 0.442, with the zeta potential value of + 31.5. The antibacterial activity result showed that the extract could inhibit the growth of Salmonella thypi, Staphylococcus aureus, and Bacillus subtilis in concentration of 500 ppm. However, the extract could not inhibit the growth of Escherichia coli in all tested concentrations. The nanoparticles showed an antibacterial activity against Staphylococcus aureus and Salmonella thypi in the concentration of 250 up to 500 ppm where as Escherichia coli and Bacillus subtilis in concentration of 500 ppm. The minimum inhibitory concentration (MIC) of the extract against Staphylococcus aureus and Bacillus subtilis were 400 ppm and against Salmonella thypi in concentration of 500 ppm. n addition, the MIC of Escherichia coli was more than 500 ppm. The MIC of the nanoparticles against Staphylococcus aureus was 300 ppm while against Bacillus subtilis and Salmonella thypi 400 ppm and against Escherichia coli 500 ppm. Accordingly, the nanoparticles have a promising strategy to formulate the extracts to improve the antibacterial activity.

Keywords: Antibacterial activity, ethanolic extract, Javanese turmeric, nanoparticles

Dr. Shirly Kumala has completed her PhD from Biomedical Faculty, University of Indonesia, Jakarta. She is the Dean of Pharmacy Faculty, Universitas Pancasila, Jakarta, Indonesia. She has published more than 25 papers both International and national journals, and has been serving as a reviewer in Journal of Pharmacy.

Brusatol Nanoparticles to Facilitate Clinical Translation for Chemotherapy

Simeon K Adesina* and Terry Elinor-Reid

Howard University, USA

Brusatol has been reported to possess a unique potential to target two distinct pathways that are important in the progression of cancers by its specific action on nuclear factor erythroid 2-related factor 2 (Nrf2) and as a global protein synthesis inhibitor. Due to its non-selective mechanisms of action, it is unlikely that brusatol can be administered as a therapeutic agent without substantial host toxicity. The oil-in-water emulsification solvent diffusion method was modified to prepare brusatol-loaded, polyethylene glycol-coated polylactide-co-glycolide nanoparticles. Scanning electron microscopy revealed the formation of nanoparticles and average size was determined by dynamic light scattering. Drug content of the nanoparticle formulation was determined by high performance liquid chromatography. The in vitro release isotherm showed a biphasic and sustained release of the encapsulated drug. Toxicity of the brusatol-loaded nanoparticles in prostate cancer cell lines was evaluated over 120 hours using the Cell Titer 96® Non-Radioactive Cell Proliferation Assay. In vitro cytotoxicity data revealed that both brusatol-loaded nanoparticles and the control brusatol solutions at the same concentrations exhibited dose-dependent toxicity to PC-3 and LNCaP prostate cancer cell lines at the concentrations used in this study with the nanoparticle formulation showing more toxicity to both cell lines. Cellular uptake of nanoparticles was evaluated using confocal microscopy after a 6-hour incubation of rhodamine-123-loaded nanoparticles with PC-3 cells. Data showed internalization of the nanoparticles. This study shows that the nanoparticle formulation of brusatol can overcome delivery challenges and facilitate the clinical translation of the compound for the treatment of cancers.

Dr. Simeon K Adesina completed his Ph.D. at the Department of Pharmaceutical Sciences, Howard University. He has published several articles in peer reviewed journals and several abstracts and conference proceedings. He has a patent and another patent submission. He joined Howard University as Assistant Professor in 2012 and is currently an Associate Professor in the Department of Pharmaceutical Sciences, College of Pharmacy at Howard University.

Microbiological and Cytological Study of the 1, 3-Bis(Alkyl)-6-Methyluracils with 1, 2, 3–and 1, 2, 4-Triazolium Moieties Fragments

A S Sapunova*, A D Voloshina, N V Kulik, A P Lubina, E S Krylova and V E Semenov

Kazan Scientific Center of Russian Academy of Sciences, Russia

Currently, the drugs used in chemotherapy do not have a desired effect, due to their low selectivity and bioavailability, as well as high toxicity, which causes many side effects.

It is known that compounds containing uracil fragment can exhibit biological activity through binding to different substrates. It is also found that the introduction of azole heterocycles leads to increased antimicrobial activity of compounds.

Previously it was shown thatthe derivatives of 1, 3-bis(alkyl)-6(5)-substituted uracil containing onium groups exhibit antimicrobial activity and low cytotoxicity in experiments on mammalian cells [1]. We have studied antimicrobial and anticancer activity, cytotoxicity and genotoxicity of new 1, 3-bis(alkyl)-6-methyluracil with 1, 2, 3- and 1, 2, 4-triazolium moieties.

The studied compounds have been tested for antimicrobial activity in relation to standard test strains of bacteria and fungi. Minimal Inhibitory Concentration of the leader compounds against Gram-positive bacteria is 0.4-4.0 mg/l and against Gram-negative bacteria - 8.0-31.3 mg/l. Antifungal activity of the investigated drugs in concentrations of 0.9-4.0 mg/l was shown.

Then the mechanism of DNA damaging effect in the SOS-lux test was investigated. The given compounds do not have genotoxic properties and showed no DNA-damaging effect.

The study of cytotoxic effect was carried out using the Cytell Cell Imaging system (GE Helthcare Life Science, Sweden). The compounds exhibiting high activity against tumor cell lines (MCF-7, A549, M-HeLa) and possessing low toxicity on normal human cell lines (WI-38 VA 13 subline 2RA, Chang liver) were identified.

The results of this work show that the investigated compounds can be considered as potential antimicrobial agents and used as key components for new drugs.

The work is financially supported by Russian Scientific Foundation (project No. 14-50-00014).

Dr. A S Sapunova is a research assistant in the International research and innovation center of neurochemistry and pharmacology of A.E. Arbuzov Institute of Organic and Physical Chemistry. In 2016 she has had started her PhD in the Microbiology laboratory, A.E. Arbuzov Institute of Organic and Physical Chemistry Subdivision of the Federal State Budgetary Institution of Science «Kazan Scientific Center of Russian Academy of Sciences», Kazan, Russia. Her main research topic is the development of new antimicrobial and anticancer drugs using new chemical compounds.”

Antimicrobial Activity and Toxicity of New Macrocyclic and Acyclic Derivatives of 1, 3-Bis(Alkyl)-Chinazoline-2, 4-Dione

A D Voloshina*, N V Kulik, A S Sapunova, A P Lubina, E S Krylova, and V E Semenov

Kazan Scientific Center of Russian Academy of Sciences, Russia

The urgency of the problem of new antimicrobial drugs development is determined by constant appearance of multi resistant micro organisms.

Previously it was shown that 1, 3-bis(alkyl)-6(5)-substituteduracilcontaining onium groups have a wide range of antimicrobial activity and low cytotoxicity in experiments on mammalian cells [1, 2 ].

We have studied antimicrobial activity, mechanism of action, cytotoxicity and genotoxicity of new macrocyclic and acyclic derivatives of 1, 3-bis(alkyl)-chinazoline-2, 4-dione. The studied compounds have been tested for antimicrobial activity in relation to standard test strains of several pathogenic bacteria andfungi. The most active compoundswere investigated against resistant strains of Staphylococcus aureus. It has been found that the main structural factor influencing antimicrobial activity of compounds is atype of an alkyl radical in the onium group.

It is shown that the macrocyclic and acyclic derivatives of 1, 3-bis(alkyl)-chinazoline-2, 4- dione have a high antibacterial activity against S. aureus strains resistant to ciprofloxacin and ammoxicillin. Antimicrobial activity against standard test strains of bacteria and fungi is manifested at the level of well-known drugs.

The investigated compounds do not exhibit genotoxicity, show low cytotoxicity to mammalian cells andinhibite the glucose dehydrogenases activity of Staphylococcus aureus 209P and Candida albicans 855-653.

Thus, a new class of biologically active compounds, which may be of significant interest for the development of new promising antimicrobial agents, was investigated.

The work is financially supported by RSF (project No.14-50-00014).

Dr. A D Voloshina is a senior researcher with PhD degree in the International research and innovation center of neurochemistry and pharmacology of A.E. Arbuzov Institute of Organic and Physical Chemistry;the head of the microbiology laboratory in A.E. Arbuzov Institute of Organic and Physical Chemistry Subdivision of the Federal State Budgetary Institution of Science “Kazan Scientific Center of Russian Academy of Sciences”, Kazan, Russia. Her professional interests focus microbiological and cytologic researches in the field of pharmacology and medicine.

Anti-Cancer Activity of the Phytochemical Indicaxanthin: In Vitro and In Vivo Studies against Melanoma

A Attanzio1*, M Allegra1, MA Livrea1, L Tesoriere1, E Panza2 and A Ianaro2

1Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Italy
2Department of Pharmacy, University of Naples “Federico II” Italy

Epidemiologic studies show promising results supporting the role of natural compounds in the chemoprevention of melanoma. Indicaxanthin is a betalain pigment from cactus pear fruit, capable of modulating specific redox-driven pathways involved in the inflammatory reaction in vitro (1). Interestingly, indicaxanthin is bioavailable and exerts strong anti-inflammatory effects when orally administered at nutritionally-relevant doses in rats (2). A causative link between inflammation and melanoma has recently been explored. In line with this, we investigated the antitumor potential of indicaxanthin vs melanoma both in vitro and in in vivo mouse model.

Indicaxanthin inhibited proliferation of human A375 melanoma cells. The inhibition measured at 24h was concentrationdependent in the range between 50 and 200 µM, with a maximum of 52% at the highest concentration. Indicaxanthin induced cell apoptosis as cytofluorimetrically revealed by double AnnexinV/PI staining. Moreover indicaxanthin time-dependently inhibited the activation of NF-kB, a transcriptional factor conferring tumor survival capacity and escape from apoptosis. In addition, the expression of Bcl-2 and c-FLIP, two inhibitors of apoptosis the expression of which is modulated by NF-kB, was decreased.

More importantly, indicaxanthin (3.2 mg/kg) orally-administered for 15 days to mice when the injected tumor had reached an average 3-4 mm diameter, induced a reduction of tumor volume (86%) and weight (83%).

Dr. A Attanzio is a Researcher in- BIO/10 Biochemistry and completed his PhD in Pharmaceutical Sciences and got a Graduate degree in Biomedicine with a vote of 110/110 and praise. He is a Patent Inventor and Guest Editor for Journal of Food Quality. and is the Author of 25 publications on international biochemical and nutraceutical journals.

Evaluation of the Antimicrobial Effect of Expired Oral Antibiotics In-Vitro

Sasha Suliman*, Dalia Abdelazim, Suzan AlZeer, Yusra Alkamali, Kawthar Algasham, HadelAlMosfir, Hessa Al Khnfri and Marwa AlHaje

Riyadh Colleges for Dentistry and Pharmacy, Saudi Arabia

Introduction: In spite of significant risks and the non-clinical importance due to loss of potency, stiff penalties against administration of expired medications are still not appropriately enforced by health policy makers in developing countries [1]

Objective: To investigate the effect of expiration on in vitro potency of oral antibiotic

Methodology: Azithromycin, Clarithromycin, levofloxacin, cloxacillin, Tetracycline, Doxycycline; both control [un expired] and investigated [expired] antibiotic were compered based on the antimicrobial potentials by challenging local isolates of different concentration of S.aureus using agar diffusion technique

Results: All Azithromycin, Clarithomycin, Levofloxacin and Cloxacillin showed significant difference (P- values: 0.005, 0.000, 0.000 and 0.001 respectively). The Difference in means of zone inhibition were 4.3mm, 7.3 mm, 8.3mm and 5.29mm respectively, which is still within the accepted efficacy range

Dr. Sasha Suliman holds an MSc degree in clinical pharmacy, from the University of Kabangsaan Malaysia (UKM), As human beings experience a disease or trauma, her great passion is bringing healing to them. She finds herself in providing knowledge to others specially, for students to help sick people getting better. So keen in building a transparent relationship with her studentsʼ because she believes that through them and she will be able to achieve her goal in healing people. There is no single approach is the right one for every individual, and got trained herfelf to deal with each individual.

Effects of Mesoglycan on Tissue Repair by Modulating Keratinocytes, Fibroblast and Endothelial Cells Functions

Antonello Petrella

Department of Pharmacy, University of Salerno, Italy

Glycosaminoglycans are polysaccharides of the extracellular matrix supporting skin wound closure. Mesoglycan is a mixture of glycosaminoglycans such as chondroitin-, dermatan-, heparan-sulfate and heparin. Glycosaminoglycans may contribute to the re-epithelialization in the skin wound healing, as components of the extracellular matrix. Here we describe, for the first time, the effects of mesoglycan in vitro cultures of adult epidermal keratinocytes and dermal fibroblasts. Once confirmed the lack of cytotoxicity by mesoglycan, we have shown the increase of S and G2 phases of fibroblasts cell cycle distribution. We further report the strong induction of cell migration rate and invasion capability on both cell lines, two key processes of wound repair. In support of these results, we found significant cytoskeletal reorganization, following the treatments with mesoglycan, as confirmed by the formation of F-actin stress fibers. Additionally, together with a significant reduction of E-cadherin, keratinocytes showed an increase of CD44 expression and the translocation of ezrin to the plasma membrane. Furthermore, as showed by immunofluorescence assay, fibroblasts treated with mesoglycan exhibited the increase of Fibroblast Activated Protein α and a remarkable change in shape and orientation, two common features of reactive stromal fibroblasts. Finally, we show the in vitro effects of mesoglycan in the new vessels formation by endothelial cells, since angiogenesis represents a key moment in wound healing. We found a strong increase of migration and invasion rates of these cells treated with mesoglycan, which mediate the activation of the pathway triggered by CD44 receptor. Interestingly, endothelial cells form longer capillary-like structures with a great number of branches, in the presence of the same treatments. Thus, the device, thanks to the mesoglycan, leads the cells to the Endothelial-to-Mesenchymal Transition, suggesting the switch to a fibroblast-like phenotype, as shown by immunofluorescence assays. In conclusion, based on these findings we suggest that mesoglycanmay be able to accelerate the healing process in venous skin ulcers, principally enhancing re-epithelialization granulation processes.

Dr. Antonello Petrella is a Professor of Pharmacology in the Department of Pharmacy at the University of Salerno, Italy. His professional interests involve the role of Annexin A1 in migration and invasion of human pancreatic carcinoma cells and in prostate cancer progression. Moreover studying the role of mesoglycan in skin wound healing. He is the Author, and has published about 60 scientific papers in refereed journals.

Overexpression of Ifnβ1 Gene in Mice Prevents Diet-Induced Obesity and its Complications in Mice

Mohammad Alsaggar1,2* and Dexi Liu2

1Jordan University of Science and Technology, Jordan
2University of Georgia, USA

The increased prevalence of obesity is raising global concerns, largely because of associated complications of the disease. In spite of significant research in the field, few therapies have been approved, and therapeutic outcomes remain insufficient. Therefore, alternative therapies are in need. Gene therapy has emerged as powerful strategy to tackle many of human diseases by modulation of gene expression levels. In this work, murine interferon beta 1 (IFNβ1)gene was overexpression using hydrodynamic gene delivery method in mice to prevent development of obesity. using diet induced obesity model in mice, we showed that IFNβ1 suppressed inflammation in adipose tissue adipose tissue hypertrophy. Also, it modulated cytokines expression toward anti-inflammatory interleukins. Importantly, IFNβ1 overexpression blocked weight gain without impacting food intake, and restored glucose homeostasis in treated mice. Together, these data suggest that IFNβ1 is a powerful anti-inflammatory cytokine with promising potential to treat inflammatory disorders. In addition, gene therapy is promising strategy to treat obesity and its related complications.

Dr. Mohammad Alsaggar is an Assistant Professor of Pharmaceutical Biotechnology and Gene Therapy from Jordan. Mohammad received his BS in pharmacy in 2009 from the Jordan University of Science and Technology (Irbid, Jordan), and his PhD in Pharmaceutical and Biomedical Sciences from University of Georgia (Georgia, USA) in 2016. Mohammadʼs research focusses on the use of gene therapy strategies for management of cancer and obesity diseases. In addition, Mohammad is working on cancer metastasis modeling using the hydrodynamic cell delivery technique for the assessment of tumor microenvironment impacts on the behavior of tumor cells growing in different organs.

Attitudes and Opinion of Hospital Pharmacists towards Extemporaneous Compounding and Related Issues in Khartoum City: Part II

Shayoub M EL*, Gubara O A, Haj Elamin AE, Ayoub MO, Tumsah M A R and Msaad A M A

Department of Pharmaceutics, Khartoum University, Sudan

Objectives: To examine the frequency, nature and extent of extemporaneous compounding undertaken by Sudanese hospital pharmacists and determine their attitude on aspects related to extemporaneous compounding.

Methods: 200 questionnaires were administered to randomly selected hospital pharmacies in Khartoum city. Feedback to most question was measures on 1-5 Likert scales. Data was collected from December 2015 to March 2016.

Results: Response rate was 60%; 75.2% were females and 24.8% were males. 28.2% of respondents compounded 1-5 prescriptions weekly that comprised 3-5% of total prescriptions; most prescriptions were dermatological preparations; major reasons for compounding were product (53%), pediatric strength 42% and official preparations 41%; Major prescribers were dermatologist; Pharmacist who often compound prescriptions; appreciable number of respondents rated standard of equipments and quality of ingredients as high, respectively; 25% and 15.8% of respondents indicated that lack of ingredients and lack of time limited their immediate extemporaneous dispensing; Factors that greatly inhibit compounding were lack of equipments, lack of practice in compounding and time constrains; 49.6% of respondents stated that demand for compounding greatly decreased over the pat few years; 52.2% of the respondents thought that, extemporaneous compounding will be decreased in the future; 54.0% of respondents felt that their skill in compounding were increased since graduation; most respondents had high confidence and professional satisfaction in extemporaneous compounding; 54% of respondents felt that their training was inadequate and emphasis should be placed in training 31, 7%; 71.2% agreed for periodical assessment of pharmacists in compounding; overall respondents felt that a refreshing course in extemporaneous compounding is useful.

Keywords: Extemporaneous, compounding, Hospital affiliation, Hospital pharmacists, attitudes, constraints, dispensing, confidence, satisfaction, reasons.

Conclusion: Extemporaneous compounding constitutes small part of hospital pharmacy activities, and respondents were strongly agreed that it should be kept within the profession. Several areas of improvement were identified and continuous education was highly demanded.

The Effect of Nutrition Program on Health Status among Dialysis Patients

Mazen A El-Sakka1*, Samah M Wadi1 and Abdalla W Al Qishawi2

1Al Azhar University-Gaza, Palestine
2Department-Ministry of Health, Al Shifa Hospital- Dialysis, Gaza-Palestine

Poor access to food among low-income adults has been recognized as a risk factor for chronic kidney disease (CKD), but there are no data for the impact of food insecurity on progression to end-stage renal disease.

Diet and anthropometrics measurements are associated with increased morbidity and mortality and a rapid deterioration of kidney function in patients with chronic kidney disease. However, there is little information regarding the effect of nutrition intervention. The aims of this study were to investigate whether of diet patterns and changes in biochemical parameters as well as eGFR among adults with CKD on dialysis, as well as, to evaluate the efficacy and safety of a nutrition education program in patients with dialysis, based on the diagnostic criteria for Protein–energy wasting. The design of the study was a 2-month Control experimental design, prospective, and interventional study. The study was started from May 2017 and expected to finish on December 2011 in the Dialysis Department of Al Shifa Hospital in Gaza, Palestine.

Subjects: A total of 133 patients with ESRD started the research study, 102 finished it and 51 subjected on very well controlled diet program.

Intervention: The 2-month nutrition education program consisted of designing an individualized diet plan based on the patientʼs initial nutritional status, and 4 nutrition education sessions.

Results and Conclusion: Promising results reveal the effectof diet program on anthropometric, biochemical, and eGFR. Further research is needed to investigate the reliability and utility of this tool in a larger population group.

Dr. Mazen A El-Sakka has completed PhD in pharmacy-Pharmacognosy, a Clinical Nutritionist Consultant, More than 30 publications, 3 Books & 10 Academic courses, 3 Patents, More than 55 international congress & workshop participations

Anti-Alopecia Activity of Hantap (Serculia coccinea Jack.) Leaves Ethanol Extract

Resmi Mustarichie1*, ImamAdiWicaksono2 and Dolih Gozali3

1Department of Pharmaceutical Analysis and Medicinal Chemistry, University of Padjadjaran, Indonesia
2Department of Pharmacology, University of Padjadjaran, Indonesia
3Department of Pharmaceutics, Faculty of Pharmacy, University of Padjadjaran, Indonesia

Objective: This study aims to determine and verify the use of ethanol extract of Serculia coccinea leaves ethanol extract as stimulant of hair growth or anti-alopecia.

Methods: The S. coccineal eaves was collected from Salawu tribe, Tasikmalaya, West Java. The extraction was done by maceration which was based on standard method of Indonesian Herbal Pharmacopeae. The viscous concentrated extract was fractionated by liquid-liquid extraction. Phytochemical screening according to the Farnsworth method. Method of hair growth on Angora type rabbit was modified of Tanaka method.

Results: The results of phytochemical screening using Farnsworth method showed the ethanol extract containing secondary metabolite of tannin compound, polyphenol, steroid, triterpenoid, quinone, monoterpenoid and sesquiterpenoid. The results of hair fertilizer testing using Tanaka method showed that ethanol extract and water extract with 20%, 15%, 10% concentration significantly could fertilize hair with test for 18 days. Extracts of ethanol with levels greater than 10% showed better results. Water fraction of 10% appeared to show the best result for rabbit hair growth overcome minoxidil.

Conclusions: This work found that the concentration of 10% ethanol extract of S. coccinea and its water fractions were affective for hair growth on male rabbits. It was suggested, however, for further study to determine the compound which was responsible by using elucidation methods and being tested to volunteers.

Keywords: Hair fertilization, ethanol extract, Sterculiacoccinea, hair grower, Alopecia, phytochemical screening

Dr. Resmi Mustarichie is Professor of Pharmaceutical Chemistry. He was graduated as PhD. Graduate supervised by Prof. Allan F.M Barton from Murdoch University, Western Australia. He is currently active as lecturer and researcher at Faculty of Pharmacy, UniversitasPadjadjaran, Indonesia, 45363. His interest in Analysis and determination of bioactive compounds from natural materials, Herbal anti-alopecia, and molecular computing