1Department of Chemistry, University of Lagos, Nigeria
2Chemistry Unit of Department of Chemical, Geological and Physical Sciences, Kwara State University, Nigeria
Background: Plant natural products have a proven global history of treating diseases and ailments. These medicinal plants have been used since ancient times in various parts of the world where access to modern medicine is limited. Medicinal plants play important role in the management of diabetes mellitus especially in developing countries where resources are limited. Diabetes mellitus (DM) is a metabolic disorder resulting from a defect in insulin secretion, insulin action, or both. Insulin deficiency leads to chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism. Diabetes mellitus affects most of the people in both developed and developing countries. The treatment of diabetes with conventional drugs is very expensive and chances of side effects are high.
Objective: The specific objective of this article is to provide a comprehensive report on on-going global efforts to discover and develop more efficacious anti-diabetic drugs with no side effect from various medicinal plants found within Nigerianʼs rich flora, which have been shown to display potent anti-hyperglycaemic activity.
Methods: Different researchers in different fields (chemistry, biochemistry and molecular biology) have employed technological developments in separation methods, hyphenated technique and high throughput assays to drive the drug discovery processes.
Conclusion: Natural products identified from medicinal plants give an exciting opportunity for the development of new therapeutic agents for the treatment of diabetes mellitus. Most prevalent among natural products are flavonoids, terpenoids, cardiac glycoside, alkaloids and steroids. Despite considerable progress in the development of synthetic drugs, the discovery of phytomedicine as an alternative therapy is progressing. This paper discusses the role of plant natural products in diabetes management.
Keywords: Medicinal plants, Natural products, Diabetes mellitus, Antioxidant activity, Anti-hyperglycaemic activity Drug discovery and development
1King Abdulaziz University, KSA
2Ain Shams University, Egypt
Moringaoleifera (MO) is a tropical drumstick tree whose various financial applications are stirring developing global interest. Kidneys vulnerable to damage bypoisons, contamination, invulnerable responses and ischemia. Intense renal failure is a continuous complexity of basic disease particularly in the inpatient setting. The point of the present study was to assess the protective and curative effect as well aschemopreventive effectiveness of M. oleifera extract against dimethylbenz(a)anthracene (DMBA) induced nephrotoxicity in rats. Rats were divided into fivegroups as follows Group (1) Control ratsgot 1 ml oral saline daily. Group (2) Renalfailure induced group. Group (3) Healthy rats got M oleifera in a dose of 200mg/Kg daily. Group (4) Rats orally treated with M oleifera in a dosage of 200 mg/kg body weight 28 days subsequent to accepting intraperitoneally dose of (DMBA). Group (5) Rats orally treated with M oleifera in a dosage of 200 mg/kg body weight 14 days before and 14 days after getting intraperitoneally dose of (DMBA). DMBA induction inspired a huge acceleration in parameters like serum urea, creatinin, protein, electrolytes, cyctatin c and β2 - Microglobulin, add up to and direct bilirubin level and MDA, with a consumption of cancer prevention agent catalysts to be specific SOD, CAT and NO. The helpful adequacy of Moringaoleifera concentrate was seen as far as standardization of changed renal oxidative stress parameters and electrolytes and both cyctatin c and β2 - Microglobulin. Explored parameters were restored, about to the ordinary qualities, after M. oleifera extract treatment. These outcomes proposed that M. oleifera concentrate could act against DMBA-impelled kidney damage in rats by a system identified with its cell reinforcement properties. So also, the oral treatment of M. oleifera, as a therapeutic effect created comparable changes to those when M. oleifera was utilized as a defensive operator, however to a lesser degree.
Keywords: MoringaOleifera, DMBA, renal failure, kidney functions, oxidative stress.
Biography:
Amal Hamza joined the Biochemistry Department at King Abulaziz University (KAU) in Saudi Arabia as an Associate Professor, on 2011. Previously, She worked as a Teaching Assistant, and as Assistant and Associate professor at the Department of Biochemistry and Nutrition, Ain-Shams University, in Egypt since 1996. She have over than 20 years of teaching and research experience. She developed and taught undergraduate classes in biochemistry and nutrition, and served on thesis and dissertation committees. Her research interest focused on studying the molecular and biochemical mechanism of natural products and essential nutrients in management and ameliorating several diseases.
1School of Pharmacy, The University of Mississippi, University, USA
2Temple University, USA
3Tafila Technical University, Jordan
With the increase in the use and abuse of opioid drugs have come an increase in the number of deaths from opioid drug overdose, including a 91% US-increase related with opioid analgesics during the period between 1999 to 2002. Opioid abuse also contributes to increased healthcare costs, which is estimated at $300 billion/year according to the White House budget office. It has been recognized that the analgesic effects and the unpleasant side effects (such as addiction, respiratory depression, and tolerance) of most therapeutic opioids are primarily due to their interaction with the mu opioid receptor (MOR). In order to counteract these negative effects, studies are underway to develop MOR antagonists. In addition to treating opioid dependence, MOR antagonists are also used in the treatment of alcoholism, and have the potential for treating a variety of other conditions such as psychosis, obesity, and Parkinsonʼs disease. Until recently, successful receptor-based drug design was extremely difficult, because the interaction between opioid drugs and the receptors were not fully understood at the molecular level. However, since reporting the crystal structure of the opioid receptors, researchers have been able to take advantage of this knowledge to discover new compounds, which target these receptors and may be useful for pharmacological and medical purposes. The current study aims to design, synthesize and biologically evaluate potential mu receptor antagonists. The preliminary virtual high throughput screening (HTS) has led to the identification of one novel small-molecule mu antagonist.
Acknowledgement: NIH-NIGMS Center of Research Excellence in Natural Product Neuroscience, grant number P20 GM104932.
Biography:
Dr. Amer Tarawneh. is Assistant Professor in medicinal chemistry at the Department of Chemistry at Tafila Technical University. He was a postdoctoral research fellow in Purdue University. Dr. Amer Tarawneh earned his doctoral degree in pharmaceutical science/ medicinal Chemistry at University of Mississippi, USA the direction of Dr. Stephen J. He obtained a Master of Science degree and a Bachelor of Chemistry degree from Mutah University in Jordan, Jordan. Dr. Amer is the authored/co-authored of over 18-refereed scientific articles as of May 2016. His research interests include drug Design and development, virtual screening for biological active compounds and natural products chemistry.
UCL School of Pharmacy, University College London, UK
Recent trends in the area of pharmaceutical products research and development appear to be directed more towards new drug delivery systems as well as new physical forms of existing APIs with enhanced properties such as polymorphs and co-crystals. Understanding the factors affecting crystallization of different polymorphic forms is highly important as good control over the conditions that produce each form is key in manufacturing pharmaceutical products. We have pioneered the use of inkjet printing to crystalise metastable polymorphic forms of pharmaceutically related materials such as mannitol, glycine and
10,11-dihydrocarbamazepine. By utilizing the unique deposition capabilities of the inkjet printing system Jetlab 4x® (Microfab Technologies Ltd, USA), droplets of size down to 100 pL were dispensed on various substrates including glass and aluminium. Phase identification was achieved by Raman microscopy, and by printing onto X-ray diffraction mounts (Micromesh™, MiTeGen) powder X-ray diffraction data were collected for crystals in droplets as small as about 5 nL. It seems that the fast evaporation rate of the printed droplets prevented the conversion of metastable forms to the stable forms, which allowed their identification. For example the most unstable form of glycine (β form) was crystallised predominantly as its solvent-mediated transformation to the stable αfrom was prevented in small printed droplets. By combining the capabilities of both inkjet printing and analytical characterization methods such as Raman microscopy and X-ray diffraction, the interesting process of crystallisation in confinement was studied where metastable forms seems to predominantly crystallise in the printed droplets. In conclusion, inkjet printing appears to provide a new approach to crystallization in confinement with great opportunities to study metastable polymorphic forms.
Biography:
Dr. Asma Buanz is a research associate at the UCL School of Pharmacy, University College London (UCL), United Kingdom. She is a pharmacist by training; obtained her BSc.(Pharm) from the University of Benghazi, Libya. She holds an MSc in Drug Delivery from the School of Pharmacy, University of London and a PhD in Pharmaceutics from UCL. She is a member of the Royal Society of Chemistry and the Academy of Pharmaceutical Sciences. Her current work focuses on utilizing the application of inkjet printing for crystallising pharmaceutically related polymorphs as part of the project “Computationally Designed Templates for Exquisite Control of Polymorphic Form” funded by the Engineering and Physical Sciences Research Council (EPSRC) in collaboration with UCL Chemistry and University of Strathclyde. She is also part of the 3D printing research group at the UCL School of Pharmacy, which focuses on developing novel 3D printed dosage forms.
1Department of Pharmaceutical Sciences and Drug Research, Punjabi University, India
2Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, India
Serotonergic interplay (with different receptor subtypes) in the cortex and hippocampus appears to be one of the important common neurochemical interplay leading to epileptogenesis, depression, learning and memory impairment. Role of different receptor subtypes of serotonin has long been implicated in epileptogenesis, depression, learning and memory impairments, but their role in epilepsy induced comorbidities is still unexplored. Therefore this study was envisaged to evaluate the role of different 5- HT receptors (5-HT 1A/2A/2C/3) in kindling induced depression learning and memory deficit.
In this study male Swiss Albino mice were kindled using subconvulsive dose of PTZ (35 mg/kg). Once the animals were kindled they were treated with vehicle, 8-OH-DPAT (1 mg/kg/day), WAY-100635 (0.3 mg/kg/day), WAY 100635 + 8-OH-DPAT, DOI (1 mg/kg/day), olanzapine (2 mg/kg/day), olanzapine + DOI, ondansetron (1 mg/kg/day; i.p.), m-CPBG (1 mg/kg/day; i.p.) and ondansetron + m- CPBG for 20 days. Seizure severity score, depression like behavior, learning and memory was evaluated on day 5, 10, 15 and 20. After the behavioral evaluations on day 20, animals were sacrificed to estimate different neurotransmitters in discrete brain parts (by HPLC-FD method), nitrite level and AChE activity (microplate reader method).
Ondansetron treatment significantly reduced the seizure severity score and improved the depression like behavior, learning and acquisition performance as compared to vehicle treated kindled animals. The effect of ondansetron was reversed by m-CPBG co-treatment. The neurochemical changes in the cortex and hippocampus also supported the behavioral outcome of the study.
This study substantiates the role of 5HT3 receptor in PTZ kindling induced depression like behavior, learning and memory deficit in mice. This study creates a rational to explore the use of more selective 5-HT3 receptor ligands for comprehensive management of depressive behavior and memory impairment in patients with epilepsy.
College of Pharmacy and Nutrition, University of Saskatchewan, Canada
In spite of significant advances in recent years towards the development of new therapies, cancer is still a largely unmet medical need and the leading cause of death in industrialised countries. The main challenge in cancer therapy is the patientsʼ immune suppression leading to tumor relapse and therapeutic failure. Chemotherapy agents are often accompanied by various side effects and poor pharmacokinetics profile. Advancements in nanoparticles as novel drug carriers are rapidly progressing and offer exciting promises. Polymeric nanoparticles have been developed and characterized to enhance the efficacy of the therapies. The drawbacks and challenges of the current cancer treatments and different strategies to overcome the issues will be presented and discussed.
Biography:
Dr. Azita Haddadi, Pharmacy doctor (Ph.D.-Pharmaceutical Sciences), is currently an Associate professor of Pharmaceutical Sciences, Division of Pharmacy, College of Pharmacy and Nutrition, University of Saskatchewan. She got her Pharm D degree in 1997 and PhD in Pharmaceutical Sciences in 2005. Dr. Azita Haddadi joined Dr. John Samuelʼs group at the University of Alberta in 2003 followed by a postdoctoral training at his laboratory working on Cancer Immunology. She got a position as senior scientist at a research based pharmaceutical company in Edmonton, AB to work on cancer therapy while she was also a Research Associate at the University of Alberta. Dr. Haddadi then joined the University of Saskatchewan as an Assistant Professor in 2010. Dr. Azita Haddadiʼs research program focuses on overcoming the ongoing challenges in cancer therapy. The main emphasis of her research is to develop new biomedical and pharmaceutical nanotechnology strategies for cancer chemo-immunotherapy. Her research attracted considerable funding from a number of national organizations in Canada.
1Faculty of Science, American University of Madaba, Jordan
2Faculty of Health Sciences, American University of Madaba, Jordan
3Department of Chemistry, The Hashemite University, Jordan
4Department of Oncology, University of Alberta, Canada
Throughout five years of research, we reported 29 examples of novel 1,5-diaryl tetrazole derivatives (typical azoles) as cyclooxygenase-2 (COX-2) inhibitors. We investigated two modes of connectivity in regards to the pharmacophore unit position and type. The inhibitory potency of the typical active azoles ranged between 1.2->100 µM toward COX-2 enzyme. The molecular docking studies of the most potent candidates showed that they are well seated inside the active site of both enzymes COX-1 and COX-2. Our recent structure-activity relationship study of a novel set of 1,5-disubstituted tetrazoles, together with the molecular docking results, proved the importance of the introduced structural modifications of the typical azoles. These modifications included using linkers with different lengths at one of the phenyl group (OH, CH2OH, CH2CH2OH) and inserting a methylene (CH2) unit between the central motif and the other phenyl group which holds the pharmacophore unit. Our bioassay screening data showed that the azole which has the CH2 spacer, the longest linker (ethyl alcohol), and the methylsulfonyl (CH3SO2) unit has the best inhibition potency for both enzymes IC50: COX-1 = > 200 µM, COX-2 = 3 µM. Further, the molecular docking studies illustrated that this azole, our lead compound, is well seated and capable of forming strong hydrogen bonds with certain amino acid residues inside the active site of the COX-2 enzyme. In the case of the COX-1 enzyme, however, the pharmacophore unit is drafted away from the active site resulting in extremely weak or no inhibition for the house keeping enzyme COX-1.
In summary, our lead compound is capable of targeting only the COX-2 enzyme, while preserving the COX-1 enzyme untouched, safe, and active.
Biography:
Since 2011, Dr. Jawabrah Al-Hourani, Baker (JB) has been employed at the American University of Madaba (AUM) in Jordan. He was awarded an early promotion to Associate Professor in 2015 based on his scientific achievements at AUM. He obtained his PhD in organic chemistry in 2005 from the Chemnitz University of Technology in Germany funded by the German Academic Exchange Service (DAAD). Between 2007–2011, he did his postdoctoral research as part of two different multidisciplinary research teams at the University of Alberta, Edmonton, Alberta, Canada, the first being at the National Institute for Nanotechnology, and the second at the Cross-Cancer Institute. Dr. JB has established his own research lab at AUM to pursue his scientific journey in diverse fields of organic chemistry, with a special focus on the synthesis of novel probes for cancer imaging and treatment. He is passionate about translational cancer research and drug design and discovery.
Dubai Pharmacy College, U.A.E.
In the present study, miconazole nitrate (MCN) was incorporated into particulate binary mixtures (PBM) using a hydrophilic polymer, poloxamer 188 (PXM), as a carrier to improve itsantimycoticactivity in comparison with the pure drug. Solvent evaporation and fusion techniques were employed to prepare series of MCN-PBMsas well physical mixtures at 1:1, 1:3, 1:5 and 1:7 ratios of MCN and PXM. MCN-PBMswere evaluated for their shape, particle size, flow ability, compressibility, mucoadhesiveness, in vitro dissolution and microbiological activity. The results revealed that a marked improvement in MCN dissolution rate was obtained from only PBMs prepared by fusion technique rather than those prepared by solvent evaporation and physical mixtures. In addition, the in vitro microbiological study showed a relevant effect where MCN-PBMsobtained by fusion method significantly enhanced inhibitory activity on yeast growth as compared to that one prepared by solvent evaporation and physical mixtures. In conclusion, the solid particulate binary mixtures prepared by fusion technique may be proposed for MCN topical applications against mycotic infections, taking advantage of the mucoadhesive and permeation enhancing properties of PXM polymer.
Biography:
Dr. Bazigha K. Abdulrasool is currently working as an Associate Professor in Department of Pharmaceutics, Dubai Pharmacy College, Dubai, United Arab Emirates. She has done her master and doctorate in Pharmaceutics at College of Pharmacy-University of Baghdad, Iraq with high research output in the area of nano particulate-peptides delivery systems. Prior to joining Dubai Pharmacy College she has taught at Baghdad University, Al-Mustansyria University and Baghdad Pharmacy Private College. Dr. Bazigha has supervised Master and Higher Diploma students for their graduation thesis. She published more than 30 research articles and abstracts in international peer reviewed journalsin the fields of drugs pharmacokinetics, advanced drug formulations, novel transdermal, buccal, ocular, and oral drug delivery systems as well as in the field of pharmaceutical education. Also she presented several posters in pharmaceutical conferences. Her research qualifications have established her as a member of editorial board and a reviewer for various international, peer reviewed scientific pharmaceutical journals. Moreover, she had been registered as a subject of the biographical record “Who is who” 2015.
1*Pioneer Pharmacy Degree College, Pioneer Medical Campus, India
G-quadruplex structures formed in telomeres and proto-oncogene represent a potentially useful target for anticancer drugs. Stabilization of this arrangement may inhibit the further action of different enzymes involved in cancer cell immortalization. In present work, structure based drug design was carried out on crystal structures of a parallel stranded human telomeric quadruplex in complex with the porphyrin TMPyP4 and tetra-(4-n-methylpyridyl) porphyrin with monomeric parallel-stranded DNA tetraplex of c-myc promoter. In case of human telomeric quadruplex, the porphyrin molecules bind by stacking onto the TTA nucleotides, either as part of the external loop structure or at the 5ʼ region of the stacked quadruplex having no direct ligand interactions with G-tetrads. This is in accord with the relative non-selectivity by porphyrin for quadruplex DNAs compared to duplex DNA. While in c-myc, promoter involves a core of three stacked guanine tetrads formed by four parallel guanine tracts with all anti guanines and a snapback 3ʼ-end syn guanine in complex with porphyrin moiety. After virtual screening some of the potential compounds were evaluated for their ability to bindand stabilise G-quadruplex structures by PCR stop assay procedure. DNApolymerase primer extension reactions were carried out using twoseparate DNA templates. One contained four repeats of the humantelomeric sequence (Quadruplex Forming, QF), Temp[TTAGGG]4 and a second contained fourrepeats of a non-G-quadruplex-forming sequence (NQF), Temp[TTAGAG]4. Primer extension reactions were conducted in the varying concentrations of porphyrin analogues. Compoundswere also evaluated for in vitro cell growth inhibition, expressed as IC50 values using MTT assay in two human tumor cell lines MCF-7 (breast carcinoma) and A549 (non-smallcell lung carcinoma). In general, all of the compounds are effective G-quadruplexstabilisers. Ligand-induced polymerase stop productsat the G-quadruplex-forming site increased upon increasing theconcentrations of ligands. The primer extension reactionsusing the non-G-quadruplex-forming Temp[TTAGAG]4had revealed no G-quadruplex stop products, which indicates that the inhibition of DNA polymerase activity using thistemplate is due to non-specific interactions of the porphyrin ligands with the DNA. It was also observed that, after comparing the inhibition of full length product formed by both quadruplex and non-quadruplex forming templates, most compounds act as non-specific inhibitors of telomerase except PYP-1 and in some extent PYP-2.
The study indicates that these compounds had strong G-Quadruplex binding affinity with very good inhibitory activity in MCF-7 and A549 cell lines.
Keywords: Telomeres, G-quadruplex, Porphyrin
Biography:
Dr. D. B. Meshram is an academician, teaching graduates and post graduates since 1998. Has worked with various educational institutes helping them to develop curriculum and research aptitude amongst students. He was awarded with junior research fellowship by University Grants Commission, New Delhi, India for pursuing his Masters in Pharmacy. His biography was published in Marquis Worlds Whoʼs Who, 2010 edition. He has guided number of students for their dissertation at postgraduate level. To his credit he has number of research publications in peer reviewed journals. He is a member of International HPTLC Association. His research interest encompasses from synthetic chemistry to analytical method development and validation. Presently he is working as a Director of Pioneer Pharmacy Degree College, Vadodara, Gujarat, India.
1Institute for Glycomics, Gold Coast Campus, Griffith University, Australia
2RCSI Royal College of Surgeons in Ireland - Medical University of Bahrain, Bahrain
Human parainfluenza virus (hPIV) is one of the leading causes of respiratory tract disease in infants and children, estimated to be responsible for one third of 5 million cases per year in the United States alone. A glycoprotein called haemagglutinin-neuraminidase (HN) at the virus envelope encompasses three key functions in virus infection and spread. The hPIV HN recognizes and attaches to sialoglycoconjugates present on the host cell and subsequently activates the fusion machinery, thereby facilitating infection. Upon virus replication, hPIV HN cleaves sialic acid from host cell receptors allowing viral spread to uninfected cells. Despite continuous efforts, neither antiviral drugs nor vaccines are approved for clinical use against parainfluenza virus to date and this reinforces the urgent need for new therapeutic discovery strategies. The viral surface glycoprotein HN represents an ideal target for the development of the urgently needed antiviral agents. We have used a multidisciplinary approach to discover designer potent inhibitors that target a novel structural feature associated with the human parainfluenza virus type 3 surface glycoprotein haemagglutinin-neuraminidase. This novel feature is the flexible 216-loop which can move to a more open form creating a cavity (the 216-cavity) that can be occupied by properly designed inhibitors. We have utilized molecular dynamics simulations to simulate binding of the newly designed inhibitors at the protein and to test their capacity to force the 216-loop open and occupy the created 216-cavity. The designed dual acting designer inhibitors represent the most potent designer compounds and efficiently block both human parainfluenza virus cell entry and virion progeny release. We have also defined the binding mode of these inhibitors in the presence of whole inactivated parainfluenza virus type 3 and recombinantly-expressed haemagglutinin-neuraminidase by Saturation Transfer Difference NMR spectroscopy. Collectively, our study provides a novel anti-parainfluenza virus pre-clinical candidate and new direction towards the discovery of potential anti-parainfluenza drugs.
Biography:
Dr. Ibrahim El-Deeb was graduated from the Faculty of Pharmacy in Mansoura University, Egypt in 2001. He earned his Masterʼs degree in Medicinal Chemistry in 2006 from the same university and in the following year (2007), he was awarded a PhD scholarship from Korea Institute of Science and Technology in South Korea. During his PhD, he worked on the development of novel kinase inhibitors as anticancer agents. In late 2010, Ibrahim joined the Institute for Glycomics at Griffith University, Australia as a postdoctoral researcher. In 2012, he was awarded a Griffith University Postdoctoral and Research Fellowship (GUPRF) to support his research with in the von Itzstein group where he led the medicinal chemistry research targeting parainfluenza virus. In September 2016, Ibrahim moved to RCSI-Bahrain where he was appointed as a lecturer in Chemistry and where he is continuing his research collaboration with the von Itzstein group in Australia.
Department of Chemistry, Science College, An-Najah National University, Palestine
New water soluble mono-cationic [Cu(dpa)2Cl]Cl and dicationic ligands mixed [Cu(dpa)(dien)]Cl2[dpa = 2,2-Dipyridylamine and dien= diethylenetriamine], were made available as Schemed. The desired complexes structure were spectral and XRD characterized. Single-crystal X-ray diffraction for [Cu(dpa)2Cl]Cl showed a distorted square pyramidal geometry around Cu(II) center. The desiredcomplexes revealed promising CT-DNA and antitumor activity against several types of cancer cells.
Biography:
Ismail Warad was born in 1973, Nablus, Palestine. He got his B. SC. and M. Sc. in Chem. from An-Najah Uni. In 2000 he won Kraduated Kullage scholarship to Tuebingen Uni., where he got his Ph. D. and Posdoc. position in organometallic chem. In 2005 he moved to work in King Saudi University-KSA as ass. Prof. at Chem. Dept. At KSU he promoted to full prof. in chemistry. 2013-until now working at ANU-Palestine. He published by now ~ 200 papers and 2 patents, 2 book chapters, supervised more than 30 graduated students. His research is in synthesis of transition metal complexes and study their catalytic activity as well as their biological application.
1Department of Pharmaceutical Chemistry, K.L.E. University College of Pharmacy, India
2KLE University, India
3College of Health Sciences, University of KwaZulu-Natal, South Africa
In this research work, a series of eighteen novel coumarinyl substituted thiazolidin-2,4-dione analogs (4a-4r) have been designed by molecular hybridization approach, synthesized and their structures were established on the basis of FTIR, 1H NMR, 13C NMR and elemental (CHN) analysis. These title compounds were screened for their cytotoxicity using MTT assay methodology against five different mammalian cancer cell lines viz. hormone dependant breast adenocarcinoma (MCF7), cervical carcinoma (HeLa), colorectal carcinoma (HT29), lung cancer (A549), prostate adeno carcinoma (PC3). The cytotoxicity screening studies revealed that MCF-7, HeLa and A549 cancer cell lines were sensitive to all the tested compounds. Though the compounds showed varying degrees of cytotoxicity in the tested cell lines, most significant effect was observed for compounds 4i (1.06, 2.4 and 3.06 µM) and 4o (0.95, 3.2 and 2.38 µM) against MCF7, HeLa and A549 cell lines respectively. In conclusion, the anticancer results of these promising leads strongly encouraged us for additional lead optimization with the aim of developing more potential anticancer agents.
Sheikh-Ul Alam Memorial Degree College Budgam, India
Natural products continue to impress drug discovery scientists by their amazing bioactivity profiles coupled with their highly complex molecular architecture. These compounds have been the principal source of anticancer chemotherapeutic agents over the last few decades. About 60-70% of the anticancer drugs which are clinically used have been either pure natural products, their synthetic or semi-synthetic derivatives. Among natural products, plant-derived compounds play a pivotal role in anticancer drug discovery programme. These plant-derived compounds include vincristine, vinblastine, camptothecin and its derivatives, etoposide, topotecan, irinotecan, paclitaxel etc. Various novel and promising anticancer drugs are currently under various phases of clinical trials. Natural products have seen many ups and downs viz-a-viz their role in cancer chemotherapy. During 90ʼs these compounds saw a dip in the top-notch pharmaceutical companies mainly because of the high throughput screening programmes which involve targeted therapies using small molecules. However, barring few cancers, these therapies were confronted with the ineffectiveness with respect to several solid tumors. This has hugely revitalized their importance in anticancer drug discovery. The current review focuses on the plant-based natural compounds and herbal extracts which specifically induce anticancer effects via the induction of apoptosis. This review also discusses their mode of action along with their botanical origin.
Gosling Research Institute for Plant Preservation, University of Guelph, Canada
Plant based medicine offers an exceptionally broad range of preventative and curative health-promoting benefits for many serious health conditions such as dementia, arthritis, cancer, cardiovascular disease, and diabetes. The synthesis and accumulation of medicinal metabolites is affected by plant genetics and environmental conditions of growth, processing and distribution, leading to enormous variability of active ingredients and poor quality of the products. Recent introduction of natural health product legislation is changing the ways in which natural health products (NHPs) are developed, manufactured, and marketed in worldwide. A range of evidences of safety, chemical consistency, and efficacy are now required for approval of all NHPs for release in the Canadian as well as US and European markets. This presentation will provide an overview of the challenges and the importance of controlled environment production to ensure product safety and efficacy of plant medicines. Integrated Plant Protection System (IPPS) is a cluster of technologies incorporating novel 3-D printed in vitro culture devices, smart bioreactors, growth chambers and greenhouses with efficient monitoring of environmental parameters and plant health for large-scale plant production. Melatonin rich plants with multiple therapeutic functions including the prevention of age-related neurological disorders will be used as a model to demonstrate the potential of IPPS to produce high quality plant based medicines. Melatonin is a mammalian neurohormone with multiple metabolic functions including neurotransmission and detoxification of reactive oxygen species. Also found in plants, melatonin and its precursor serotonin are believed to play a therapeutic role in sleep disorders, depression, Alzheimerʼs, Parkinsonʼs, and Huntingtonʼs diseases in addition to aging and cancer. The IPPS has facilitated our research on rapid detection and optimization of melatonin in a range of neurologically active medicinal plants such as Hypericum, Echinacea, Scutellaria, Datura, and Salvia, as well as the discovery of novel medicinal compounds. The IPPS integrated approaches may redefine the ways in which the future plant medicines will be developed, manufactured, and marketed.
Biography:
Praveen K Saxena is a Professor at the University of Guelph, Canada since 1989. The focus of research in Dr Saxenaʼs Lab has been on developing value- added products and production technologies for the Canadian agricultural and horticultural industries. Significant contributions of his research include the development of optimized production technologies for medicinal plants and the conservation and sustainable use of endangered plant species that are traditionally used in medicinal, religious, spiritual and cultural practices. Dr Saxena has contributed more than 170 research papers in peer reviewed journals, edited four books, and served as editor and reviewer for many journals. He has supervised over 50 graduate students, postdoctoral fellows and technical assistants. Dr. Saxena also teaches a number of courses in areas of Plant Propagation, Biotechnology, and Medicinal Plants. His other interests include exploring the role of yoga and spirituality in human health. As the director of the Gosling Research Institute for Plant Preservation (GRIPP), Dr. Saxena manages research and teaching activities for GRIPP as well as industry collaborations, through national and international collaborations on the use of biotechnologies for plant conservation and commercial propagation.
Spectrum Institute of Pharmaceutical Sciences and Research, India
In the present scenario there is a need to evolve an eco-friendly processes for the synthesis of nanoparticles. The researchers are changing their focus from physical and chemical processes towards ‘green’ chemistry and bioprocesses. These processes not only help in health benefits in various ways such as :-
1) Clean water with less release of hazardous chemical wastes to water posing many diseases.
2) Safe environment for workers of chemical industry ie less fire and explosion damages
3) Less impure air:- Release of hazardous chemicals in air.
4) Safe consumer products will be synthesised.
5) Safe food as the hazardous chemicals which enter food chain will be less.
In nano particle synthesis the increase in the surface area helps to increase surface energy and catalytic reactivity further increases which improves the effectiveness of nanoparticles. The synthesis of nanoparticle can be done by various techniques but the biological approach for the synthesis of nanoparticles become imperative. The advantage over the other biological processes are less elaborate process of maintaining cell culture with so many precautions and handling care.
In the present research the various plant species are taken into consideration using this beneficial technique. The process of synthesis of silver nanoparticles will be by the reduction of aqueous Au3+ ions with the aqueous extract of various plant species.
University of St Andrews, Biomedical Sciences Research Complex, United Kingdom
Neurodegenerative diseases have multiple and often common mechanisms in their aetiologies. These multifactorial aspects have driven the search for multi-target drugs for use in therapy. Inhibition of monoamine oxidase (MAO) in the brain is a well-established way to increase neurotransmitter levels, so is a commonly desired target for multi-target designed ligands (MTDL). Screening for MAO inhibition is not straightforward, so some of the interesting physiological and chemical features of these enzymes will be discussed, along with the different roles, locations, and kinetic properties of MAO A and MAO B. Examples of recent multitarget compounds designed to combat Alzheimerʼs Disease will be given.
In addition to slowing the breakdown of the neurotransmitters, MAO inhibitors (MAOI) and decrease oxidative stress by stopping the production of its second product, H2O2, that causes oxidative damage to mitochondria. Mitochondria are vital to healthy neurons to produce sufficient ATP to support the cycles of neurotransmitter release and reuptake, as well as to maintain a healthy cell. Multitarget compounds for Alzheimerʼs disease treatment that inhibit both cholinesterases (for cognitive function) and monoamine oxidases (a proven anti-depressant strategy), can also act as antioxidants to protect mitochondrial function. New compounds were assessed against the individual targets and on cell survival and mitochondrial function in the cell. Some MAOI were assessed in a cellular model of neurodegeneration, namely in fully differentiated SH-SY5Y neurons were treated with homocysteic acid (HCA), an analogue of the neurotransmitter glutamate shown to induce neurodegenerative pathology. Cell viability was decreased by HCA but rescued by the MAOI. HCA treatment significantly decreased the proportion of normal mitochondria and increased the proportion of rounded and interconnected mitochondria, but MAOI gave some protection, decreasing the proportion of rounded mitochondria. These effects indicate that the mechanism of MAOI in the treatment of neurodegeneration is not just to spare the neurotransmitters.
Biography:
Rona R. Ramsay studied at the Universities of Edinburgh and Cambridge, held a Beit fellowship in Cambridge, and progressed to the full research professor level the University of California San Francisco before moving to her current position at the University of St Andrews in 1995. After discovering the mitochondrial carnitine carrier, her research has focused on mitochondrial enzymes, applying techniques of kinetic analysis, inhibitor studies, protein chemistry, and molecular biology to investigate how enzymes work and how they are regulated. Research areas include fatty acid metabolism, flavoenzymes and redox carriers, the mechanism of MPTP toxicity to mitochondria, and drug design formonoamine oxidases (current). Current collaborations across Europe aim to design multifunctional anti-neurodegenerative drugs.
Rajiv Gandhi University, India
Arunachal Pradesh State in Northeast India is inhabited by 28 major tribes and about 110 sub-tribes with rich treasure of indigenous knowledge. Diarrhea is one of the commonest diseases in the state. In remote villages, medicinal plants are an integral source of therapeutic drugs and play a significant role as easily available remedy among the rural folk. A good number of anti-diarrheal plants (viz., Manihotesculenta, Musa paradisiaca, Ocimum sanctum, Piper betel, Spilanthesacmela, Terminaliachebula, Terminaliamyriocarpaand Piper mullesua) were reported where leaf was the most preferred plant part. Of late, however, folk medicine is no more an attraction to the younger generations and is seriously threatened due to deforestation, environmental degradation and acculturation, currently taking place in the state. Documentation through ethnobotanical studies, nevertheless, is critical for conservation and utilization of this indigenous knowledge. It is worth mentioning that men, elder people and illiterate ones had better knowledge on medicinal plants use as compared to women, younger and literate people. Findings of this documentation study can be used as an ethnopharmacological basis for selecting plants for future phytochemical and pharmaceutical studies.
Federal Ministry of Science and Technology, Abuja, Nigeria
Tuberculosis (TB) is a dangerous disease that has killed several millions of people globally in recent times. The available drugs for the treatment of the disease are not effective for complete cure and in most cases, usually come with side effects, as a result of which new set of potent drugs are needed.
In a quest to develop potent hit/drug leads for TB, betulinic acid (BA) and oleanolic acid (OA) were isolated respectively from Curtisiadentata and Syzigumaromaticum. The 3-O- Acetyl analogue of BA and OA were synthesized. The cinnamic acid conjugates at C-28 position of the four (4) synthesized compounds were all characterized using IR, MS and 1H and 13C NMR.
All the test compounds exhibited anti-TB activity, albeit to different levels of efficacy. The MIC values of the two pentacyclictriterpenes (BA and OA) against the mycobacterium ranged from >109.48uM and 42.04uM respectively. The acetylation of BA and OA at C-3 position did not observably improve their activity (MIC value of 39.70uM and 100.26uM) andneither did the cinnamic acid ester of BA and OA at C-28 position enhance the anti-TB activity (MIC value of >85.20uM and 48.05uM respectively). The di-substituted, 3-O-Acetyl and 28- cinnamic acid ester of BA and OA however exhibited some enhanced anti-TB activity with MIC value of 17.88uM.
Biography:
Victor Olugbenga Fadipe completed his PhD degree in Organic Chemistry (Natural product/Synthesis) at University of Zululand, KwaDlangenzwa, South Africa. He has more than 10 papers in reputable Journals. His research interest is in the bioprospecting for drug lead candidate for infectious tropical diseases from medicinal plant. He is a member of several learned society in chemistry.
The University of Jordan, Queen Rania Street, Jordan
Hypocholesterolemic activity of Crataegus aronia L. (Rosaceae) is therapeutically praised. Its potent antiobesity (P<0.001, n=6-8) as well as marked triacylglycerol-reducing efficacies (P<0.001, n=6-8) in 10 weeks-high cholesterol diet (HCD) fed rats are demonstrated. Pancreatic triacylglycerol lipase (PL), α-amylase and α-glucosidase are an interesting pharmacological target for the management of dyslipidemia, atherosclerosis, diabetes and obesity. Comparable to acarbose, acute starch induced postprandial hyperglycaemia as well glycemic excursions in normoglycemic overnight fasting rats was highly significantly (P<0.001) dampened by C. aronia 100, 200 and 400 mg/Kg b.wt aqueous extracts (AE), but not acute glucose evoked postprandial hyperglycaemia increments, unlike diabetes pharmacotherapeutics metformin and glipizide. C. aronia aerial parts as well as fruits AEs (0.1-10 mg/mL) were identified as in vitro dual inhibitors of α-amylase and α-glucosidase with respective IC50 (mg/mL) of 2.1 ± 0.3 and 3.5 ± 0.7. Still, it lacked on in vitro hindrance of glucose movement, dissimilar to guar gum. Equivalent to orlistat (PL IC50 of 0.1 ± 0.0 µg/mL), C. aronia tested AEs and its purified bioactive phytoconstituents; quercetin and rutin inhibited highly substantially in a dose dependent trend PL in vitro (n=3), in an ascending order of obtained PL- IC50 (µg/mL): quercetin; 30.1 ± 2.8, rutin; 77.3 ± 11.7, C. aronia aerial parts; 225.2 ± 33.4 and C. aronia fruits; 286.1 ± 37.4. Flavonoid-rich C. aronia, as a functional food and a nutraceutical, modulating gastrointestinal carbohydrate and lipid digestion and absorption, maybe be advocated as an exquisite and potential candidate for combinatorial obesity-diabetes prevention and phytotherapy.
Keywords: Crataegus aronia, Rosaceae, pancreatic lipase, enzymatic starch digestion, high cholesterol diet, flavonoids
Biography:
Violet Kasabri, PhD, MSc, is a Biomedical Associate Professor at The University of Jordan. Dr Kasabri has over 30 PUBLICATIONS between peer reviewed journal articles and book chapters. She is an internationally recognized expert in many areas of natural product based therapeutics of Diabetes, Obesity and Cancer, in addition to her research and projects in Clinical Research and Drug Discovery. She is a regularly sought after and requested lecturer at the National, Regional and International Symposiums. Dr Kasabri is a regularly and frequently invited reviewer for numerous International journals with relevant fields of expertise. Her Recent publications include a paper on the use of Salvia species as efficacious anti-diabesity agents in addition to her work with pancreatic proliferative natural products as therapeutic regenerative agents. Dr Kasabri is a faculty member at the Faculty of Pharmacy, Dept. of Clinical Pharmacy-The University of Jordan where she routinely lectures on various topics related to Clinical Biochemistry. She has served as a member of various scientific societies and acted on a number of institutional committees including the Editorial Committee of the 15th Scientific Congress of the Association of Pharmacy Colleges in the Arab world. Dr. Kasabri is recognized by her peers as a scientific expert that integrates new technologies into everyday practices. Dr. Kasabri has been investigating the effectiveness and utility of natural products into preventive medicine of diabesity and cancer for the past years. Dr. Kasabri holds a BSc with highest honors in Biomedical Sciences from The University of Jordan. She completed her Masters with Distinction as well as her PhD in Biomedical Sciences from University of Ulster, N. Ireland, UK.
Department of Pharmacy, Birla Institute of Technology and Science-Pilani, India
Purpose: Adenosine receptors (AR) play an important role in chemical signaling in both, peripheral and central nervous systems. Four subtypes of Adenosine Receptors have been identified: designated A1, A2A, A2B, and A3. A2A ARs are found in high density in certain brain regions, such as Striatum, Nucleus accumbens, and Olfactory tubercle. Adenosine exhibits high affinity to A2A ARs, which appear to be tonically activated under physiological conditions. A2A AR antagonists have been proposed as novel therapeutics for Epilepsy and Parkinsonʼs disease.
Methods: Human A2A AR bound to ZM241385 with IC50 0.22nM (PDB ID: 3EML) crystal coordinates were downloaded from protein data bank. Energy-optimized pharmacophore was prepared using Schrodinger software. The resulting pharmacophore model contains one hydrogen bond Acceptor (A), one hydrogen bond Donor (D) and three Ring systems (R). Using these features, screened against the public library of compounds (Asinex) to find potential lead compounds.
Results: The compounds which yielded fitness score of more than 1.0 the pharmacophore model were further subjected to Glide HTVS, SP and XP. Glide docking results revealed 33 hits were identified as potential lead molecules. Among them 9 Asinex molecules were selected based on the highest docking score and more number of hydrogen bonds with Glu169, Asn253 amino acids and Compounds were evaluated in the PTZ induced seizure model in adult zebrafish (standard 8 min. protocol). Furthermore most potent compounds were evaluated for Dose response analysis and major toxicities in Zebrafish model.
Conclusions: This study demonstrates that a pharmacophore search using a model based on A2A AR inhibition, and the enzymeʼs structural features can be used to screen for new candidates for antiepileptic therapy. Most potent compound to show Anti-epileptic activity was selected and derivatives are synthesized to develop SAR. These have to be validated by using In vitro inhibitory activity.
Department of Biological Sciences, Ahmadu Bello University, Nigeria
The in vitro antimalarial activity of the crude methanol extract of Urelytrum giganteum used by traditional healers in Zaria, Nigeria for malaria treatment was screened against the erythrocyte stages of Plasmodium falciparum (strains 3D7 and FCR3). The screening methodology involved using the Malaria SYBR Green I- based fluorescence assay (MSF) for 3D7 strain, parasite lactate dehydrogenase (pLDH) colorimetric enzyme assay for FCR3 strain and haemolysis assay used as a cytotoxicity test for the crude extract. The crude extract and fractions obtained from non-polar and polar column elutions were dissolved in a non- lethal DMSO concentration (0.013%), serially diluted and added to ring stage of P. falciparum (200µl at 1 % parasitemia, 2 % hematocrit) with chloroquine (0.5µM, as control) and incubated at 37°C static for 96 hrs. This crude extract showed an IC50 of 6.78± 0.78µg/ml against 3D7 strain, IC50 of 6.70± 0.82µg/ml against FCR3 strain and only five column fractions from the fractions tested showed the highest activity against the parasite with notable IC50 values of 2.74, 2.05, 5.00, 1.46 and 3.96 µg/ml. The compounds phenyl propanoid and free fatty acids were identified from these fractions using GC-MS. Moreover, this crude extract exhibited no haemolytic activity at concentrations of 5 and 1 µg/ml against human erythrocytes. The outcome of these evaluations seems to support the basis for the traditional use of this plant in the management of malarial by ethno medicinal practitioners. However, further toxicity studies are encouraged to be carried out before this extract can find use in clinical management of malaria.
Keywords: MSF, pLDH, antimalarial, cytotoxicity, GC-MS, Urelytrum giganteum
Institute of Pharmacy, Nirma University, India
Cancer is 2nd major and deadliest disease after metabolic disorder. There are approximately 1,665,540 new cases of all cancer sited in 2014 and an estimated of 585,720 people died. We carried out extensive literature search on Aurora Kinase, which is one of the vital target in the treatment of cancer. Hence, present research efforts were made todiscover potent molecules against Aurora kinase inhibition for cancer treatment. Based on preliminary computational study, structural importance of pteridine moiety in highest QFIT value molecule of virtual hit; it was selectedas a core moiety for further designing of molecules. 20 substituted pteridinederivatives were designed, synthesized and characterised by 1H and 13C NMR, mass andelemental analysis, while purity was checked by HPLC. All these compounds were evaluatedfor in vitro studies on five cancer lines; from which, compoundswere found potent, specifically on cancer cell line. Based upon results of in vitro studies, they wereselected further, along with 5-FU, for in vivo study by cancer model on mice. Compound showed favourable actions against cancer and treated tumoursdemonstrating micro molar potential of the series. This study could be explored in future to design lead molecule for the treatment of cancer.
Biography:
Ankit Borisa is a Ph.D Research Scholar of M.Pharma, Medical Chemistry in Department of pharmaceutical chemistry, Institute of pharmacy, Nirma University, Ahmedabad City, Gujrat state, India.-382481
Mashhad University of Medical Sciences, Mashhad, Iran
Retinoblastoma(Rb) is known as a rare form of cancer that rapidly develops from the immature cells of a retina. This article focuses on a very important aspect of Rbbased on biomarker discovery covers the pros and cons of using miRNAs as important prognostics, diagnostics and therapeutics biomarkers for this deadly disease. Proper monitoring and treatment are the cornerstones for the improvement of Rb outcomes. Several lines of evidence have shown that miRNAs can affect various pathogic events involved in Rb. The miRNAs regulate more than one hundred gene targets, on the other hand, one gene can also be regulated by a number of miRNAs. These molecules can serve as diagnostic, prognostic and therapeutic biomarkers in various stage of Rb. Here, we highlighted the state of the art for both discovered miRNAs as biomarkers and also future need to ascertain if the use of miRNAs in combination with different systemic and conventional biomarkers and therapies would result in improved outcomes of Rb patients.
BharatiVidyapeethʼs College of Pharmacy, India
Thiazolidinediones (TZDs)viz., troglitazone, rosiglitazone and pioglitazone, were explored for their antidiabetic activity are now being unearthed for their anticancer activity. This is evident by the recent reports suggesting that these agents help in eradicating leukemic stem cells in combination with imatinib. However, these known TZDs cause several side effects and these have been attributed to their ability to activate peroxisome proliferative activated receptor γ (PPARγ) receptor. To evade the toxicity we rationally designed and synthesized TZD containing moieties (3a-3y) which would spare PPARγ. Synthesized molecules were screened on various malignant cell lines using SRB assay. Almost all moieties exhibited GI50activity on breast (MCF-7), oral (GURAV) and leukemia (K-562) cell lines in the range of 0.5µM- 80µM. Imatinib, a gold standard for chronic myeloid leukemia (CML)has started gaining resistance. Considering the recent reports on known TZDs in CMLpatients and resistance issue, we further continued our work with K562 cell line. Few molecules were found to arrest G0/G1 phase of cell cycle in dose(5 µM, 10 µM, 25 µM and 40 µM) and time dependent manner (at 10 µM and 20 µM). Two leads 3t and 3x were selected and further found to inhibit cyclin D1 and proliferating cell nuclear antigen (PCNA) at 10 µM and 20 µM using immunoblotting assay. The pharmacokinetic studies of these two derivatives were studied and reported. Moieties were further evaluated for in-vivo tumor regression activity alone and in combination with imatinib in nude mice. Molecules substantially reduced the tumor size in combination with imatinib.
Biography:
Hardik Joshi is a Ph D senior research fellow worked on a project funded by Basic Research in Nuclear Sciences (BRNS), India in collaboration with Tata Memoriaʼs Advance Centre for Research and Education in Cancer (ACTREC). Mr. Joshi worked on design, synthesis and biological evaluation of novel thiazolidinediones and its bioisosteres as anticancer agents. He has presented parts of his research work at various international platforms and has published review and research articles in esteemed journals.
Faculty of Pharmacy, Yeditepe University, Turkey
Cancer results from unregulated cell growth. Reactivating cell death in cancer cells, i.e. apoptosis, is a classical anticancer therapeutic strategy. Theapoptosis-inducerproperty of the (2RS,4R)-2-phenyl-3-propinoyl-thiazolidine-4-carboxylic acidethyl ester (ALC67) molecule has been discovered recently1,2. Toelucidate the mechanism of action of this molecule and to evaluate the impact of the phenyl group that the thiazolidine ring presents at its second position on thecytotoxicity, we developed derivatives ALC 67 analogues replacing the phenylmoiety with various aliphatic and aromatic groups.
Thecyto toxic activity of thenovel (2RS,4R)-2-phenyl-3-propinoyl-thiazolidine-4-carboxylic acidethyl ester derivatives were evaluated on humanliver HUH7 and Mahlavuhepato cellular carcinoma cell (HCC) lines with the sulforhodamine B (SRB) assay. Results demonstrated that the antiproliferative property was conserved when the phenylmoiety was replaced.
Since the mutagenic and genotoxic properties of marketed anticancer molecules constitute a main issue to be addressed, then we fosuced on the analysis of the mutagenecity, antimutagenecity and genotoxicity of ALC67 molecule which has promissing antiproliferative activity3. Themutagenicity and antimutagenicity of ALC67 were evaluated by Ames test performed on Salmonella TA98 and TA100 strains. Thegenotoxicity of this molecule was investigated in the chromosomalaberrationassay on humanlymphocytes. All results revealed that the analyzed structure is not mutagenic in two Salmonella strains tested and was not genotoxic in humanly mphocytes in vitro. All these results indicate that after performing some more mutagenicityassay using other recommended strains, this compound can be safely used for the development of new structures exhibiting anticancer activities.
1Department of Information Technology, Kumaun University, India
2Department of Statistics, Kumaun University, India
3Department of Botany, Kumaun University, India
4School of Computational and Integrative Sciences, Jawaharlal Nehru University, India
In present work, we used three machine learning classifiers: Random Forest, Decision Tree, and Support Vector Machine to build three predictive models of an anti-mycobacterial dataset obtained from ChEMBL database and evaluated for their predictive capability. Based on the statistical evaluation, Random forest model showed the slightly higher area under the curve (AUC), better accuracy, sensitivity, and specificity in the cross-validation tests as compared to Decision Tree and Support Vector Machine. The statistical results indicated that the Random Forest model was the best predictive model with 93.83% accuracy, 98.4% ROC, Decision tree model came out to be the second with 92.8% accuracy, 95.2% ROC and the SVM model was found to be last with 90.64% accuracy, 93.8% ROC. Additionally, we built toxicity prediction models on the Single Cell call DSSTox carcinogenicity database (AID1189) using machine learning classifiers. The result showed that the Random Forest model was the best predictive model based on zero toxicity tolerance. We deployed the anti-mycobacterial and toxicity prediction models were on ChEMBL anti-malarial dataset containing 1.5 lakh compounds and a dataset of 1554 approved drugs resulting 27705 and 1554 compounds respectively as nontoxic anti-mycobacterial compounds. Thus machine learning models present highly efficient methods to find out novel hit anti-mycobacterial compounds. We suggest that such machine learning techniques could be very useful to screen drug candidates not only for tuberculosis but also for other diseases.
1Department of Information Technology, Kumaun University, India
2Department of Statistics, Kumaun University, India
3Department of Botany, Kumaun University, India
4School of Computational and Integrative Sciences, Jawaharlal Nehru University, India
Machine learning techniques are advanced computational techniques which can be used to build a predictive model of compounds dataset to find out important features to predict a specific biologicalactivity from unknown compounds and design better drugs. In present study, several QSAR models were constructed by using machine learning approaches on three different datasets ChEMBL3132000, ChEMBL907779, and AID 43299of InhA, the enoyl-acyl carrier protein reductase (ENR) from Mycobacterium tuberculosis (Mtb) is one of the key enzymes involved in the mycobacterial fatty acid elongation cycle and has been validated as an effective antimicrobial target. The best QSAR models were built with excellent values of statistical matrices from each dataset and deployed on a data set of 1450 approved drug from drug bank. Amoxicillin found to be highest predicted activity 6.54 pIC50, and Itraconazole is second highest predicted activity 6.4 pIC50 calculated based on the RF model using CFS-GS-FW descriptor set in the dataset of ChEMBL997779 of InhAMtb. The RF QSAR model predicted several potential drugs which could be novel InhAMtb inhibitors. Additionally, Molecular docking identified top-ranked 10 approved drugs as antitubercular hits showing G-scores-8.23 to -6.95(in kcal/mol). Further, high throughput virtual screening identified top 10 compounds as antitubercular leads showing G-scores -9.26 to -8.24 (in kcal/mol), compared with control compoundsG-scores -7.86 to -6.68 (in kcal/mol) which are known antitubercularInhAMtb inhibitors (ChEMBL907779:DS2 dataset). This result indicates these novel compounds have the best binding affinity for InhAMtb. Among this studies, we conclude that machine learning based QSAR models can be useful for the development of novel target specific antitubercular compounds.
Moulay Ismail University, Morocco
The present wok aims to evaluate the cardiovascular effect of Nigella sativa L. aqueous extract (NSAE) in normal rats. The in vivo experiment showed that the intravenous injection of NSAE at the doses of 50, 100 and 200 mg/kg of body weight produced a dose dependent reduction in the mean arterial blood pressure (MABP) (p<0.001) accompanied by a significant fall in heart rate (p<0.01). In the in vitro experiment, NSAE was tested at the doses of 10, 20 and 30 mg/ml. Addition of NSAE to the plateau contraction induced by Norepinephrine (NE) produced a dose dependent reduction in the arterial tone (p<0.01). Furthermore, incubation of NSAE during 30 min caused a right shift of the contraction response curve of aortic ring to NE with a reduction of the maximal contraction response (p<0.01). Endothelium destruction significantly reduced the vasorelaxant effect of NSAE at a dose of 30 mg/ml (p<0.01). Furthermore, Nitric oxide synthase inhibitor: Nw-Nitro-L-Argenine Methyl (L-NAME) produced a significant reduction (p<0.01) of the in vitro vasorelaxant effect of NSAE at a dose of 30 mg/ml.
We conclude that NSAE possess a rapid and dose dependent in vivo hypotensive effect in normal rats which may be probably due to the inhibition of parasympathetic tone. In isolated aortic ring, NSAE possess a potent inhibitor of contractile response to NE which may be probably due to an increase in the endothelial nitric oxide synthesis.
This work was supported by the CNRST under grant N° PPR/2015/35.
Biography:
Mohamed Eddouks is Professor at Moulay Ismail University, Faculty of Sciences and Techniques Errachidia, Morocco. He is a researcher in Physiology and Pharmacology with a Master Degree in Metabolic and Molecular Endocrinology from University of Paris vi, a specialized certificate in Endocrine Pharmacology from University of Paris vii and PhD degrees in Physiology and Pharmacology from University of Liege, Belgium and Sidi Mohammed Ben Abdellah University, Fez, Morocco. After his post-doctoral fellowship at Department of Physiology, Faculty of Medicine of Montreal, Canada, he is working for the last 16 years on medicinal plants. His work on antidiabetic and antihypertensive plants is well recognized globally. His research focuses on ethno biological as well as pharmacological issues in the use of Moroccan medicinal plants for the treatment of diabetes mellitus, obesity and hypertension. His contribution to this field includes four international books and more than 80 peer-reviewed articles and book chapters of international repute. He is Guest Editor of American Journal of Pharmacology and Toxicology, Lead Guest Editor of an annual special issue published by Evidence-Based and Complementary Alternative Medicine, Regional Editor of the Following journals: American Journal of Food Technology, Journal of Applied Sciences, Trends in Applied Sciences Research and Singapore Journal of Scientific research, Member of Editorial Board of several international journals. He has been honored with the first Prize of Scientific Research in 2008 by the Moroccan Association of Research and Development and the first Prize of the Federation of Arab Scientific Councils in 2016. He has been the Dean of Polydisciplinary Faculty of Errachidia from 2008 to 2012.
Moulay Ismail University, Morocco
The purpose of this study was to investigate the effect of a single dose and daily oral administration for seven days of the aerial part aqueous extract (A.P.A.E) of Tamarix articulata Vahl. (T. articulata) at a dose of 5 mg/kg body weight on blood glucose levels in both normal and streptozotocin-induced diabetic rats (STZ). Single oral administration of T. articulata A.P.A.E reduced blood glucose levels 6 h after administration in normal rats and STZ diabetic rats (p<0.0001). Furthermore, blood glucose levels were decreased in both normal and STZ diabetic rats after seven days of treatment (p<0.0001). Moreover, no significant changes in body weight in normal and STZ rats were shown. According to the oral glucose tolerance test, the aqueous extract of T. articulata (20 mg/kg) was shown to improve significantly the increase on blood glucose levels in normal treated rats (p<0.001) 90 min after glucose administration as compared to the control groups. Finally, histopathological analysis revealed the beneficial effect of T. articulata on pancreas and liver. In conclusion, this study demonstrates antihyperglycemic and hypoglycemic affects of T. articulata in severe diabetic state thus warrants further investigation on its major compounds with in depth mechanistic studies.
Keywords: Tamarix articulata; Streptozotocin; Histopathological changes; Liver; Pancreas; Aqueous extract; Glucose tolerance; Blood glucose.
Funding: This work was supported by the CNRST under grant n° PPR/2015/35.
Biography:
Mohamed Eddouks is Professor at Moulay Ismail University, Faculty of Sciences and Techniques Errachidia, Morocco. He is a researcher in Physiology and Pharmacology with a Master Degree in Metabolic and Molecular Endocrinology from University of Paris vi, a specialized certificate in Endocrine Pharmacology from University of Paris vii and PhD degrees in Physiology and Pharmacology from University of Liege, Belgium and Sidi Mohammed Ben Abdellah University, Fez, Morocco. After his post-doctoral fellowship at Department of Physiology, Faculty of Medicine of Montreal, Canada, he is working for the last 16 years on medicinal plants. His work on antidiabetic and antihypertensive plants is well recognized globally. His research focuses on ethno biological as well as pharmacological issues in the use of Moroccan medicinal plants for the treatment of diabetes mellitus, obesity and hypertension. His contribution to this field includes four international books and more than 80 peer-reviewed articles and book chapters of international repute. He is Guest Editor of American Journal of Pharmacology and Toxicology, Lead Guest Editor of an annual special issue published by Evidence-Based and Complementary Alternative Medicine, Regional Editor of the Following journals: American Journal of Food Technology, Journal of Applied Sciences, Trends in Applied Sciences Research and Singapore Journal of Scientific research, Member of Editorial Board of several international journals. He has been honored with the first Prize of Scientific Research in 2008 by the Moroccan Association of Research and Development and the first Prize of the Federation of Arab Scientific Councils in 2016. He has been the Dean of Polydisciplinary Faculty of Errachidia from 2008 to 2012.
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, UK
Type 2 diabetes mellitus is a worldwide chronic disorder which is characterised by insulin resistance and high blood glucose levels (1). The treatment of type 2 diabetes involves the use of traditional oral antidiabetic agents, such as sulphonylurea or glibenclamide, metformin, and/or insulin (2). However, incidence of the disease is increasing in many parts of the world which means novel antidiabetic agents are needed.
Recently, new types of oral antidiabetic agents that inhibit DPP-IV have been developed and one has been approved for medical use. Collaboration between Strathclyde Innovations in Drug Research (SIDR) and the Drug Discovery Portal (DDP) using a combination of virtual and high throughput screening identified a novel hit (AM11) against DPP-IV. The aim of this project was to modify AM11 to see if inhibition against DPP-IV could be improved.
Compounds with a range of activities against DPP-IV were prepared, but all had comparable or lower activity than AM11. Docking studies were performed to explain the structure-activity relationship profiles of the different libraries prepared.
Department of Chemistry, Birla Institute of Technology and Science, Pilani, India
Cancer is a class of genetic disease caused by disregulation of various cellular pathways that orchestrate cell growth and death. Chemotherapy is the major technique to treat various types of cancers. Unfortunately it is associated with severe side effects. To improve the drug selectivity, researchers started exploring several new avenues and combination oftwo or more pharmacophores is one such approach.
Azaindoles and 1,2,3-triazoles are imperative class of heterocyclics and play a major role in medicinal chemistry. Several of these were found to have anti-cancer and anti-angiogenic properties. Several pharmacophores like naphthofuranones, methoxyphenyl oximes, and piperazinylindenoquinolinone having oxime (hydroxylamino) as a functional group display very good anticancer activity (Fig 1). A series of novel 1, 2, 3-triazole derivatives of 7-azaindole (5A-O) were synthesized (Scheme 1) and screened for their in vitro cytotoxicityagainst MDA MB-231(breast), A549(Lung) and HeLa(cervical) cancer cell lines, by sulforhodamine B assay method. All the synthesized compounds exhibited antiproliferative activity with GI50 values ranging from 0.12 to 9.84 µM. It is observed that, majority of the compounds displayed significant growth inhibition on A549 and MDA MB 231 cancer cell lines as compared to HeLa cancer cell line. Compounds 5d and 5k showed potent activity against A549 with GI50 values 0.12 µMand 0.16 µM while the positive controls, doxorubicin and paclitaxel demonstrated the GI50 in the range of 0.01-0.09 µM and < 0.01-0.023 µM respectively. These derivatives were also subjected to molecular docking study to investigate the mode of binding by using ALK (Human anaplastic lymphoma kinase) enzyme using Schrodinger suite 2013.
Biography:
Surendar Chitti have completed my masterʼs degree in organic chemistry (2006) from Kakatiya University, Telangana, India. After that, he worked as research chemist at various R&D centers situated in India. Overall he has 8 years of industrial R&D experience. Presently, he pursuing his PhD with Prof. K.V.G. Chandra Sekhar at BITS Pilani Hyderabad Campus, Telangana, India.
1Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
2Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Background: Oxidative stress has a key role in development of type II diabetes mellitus (T2DM). There has been considerable evidence confirmingcurcuminʼs antioxidant properties. The aim of this study was to assess the effects of curcumin on oxidative indicesindiabetic individuals.
Methods:Diabetic subjects were randomly assigned to curcumin (1 g/day) plus piperine (10 mg/day) or placebo for a period of 3 months. Serum levels of malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidant capacity (TAC) were measured at baseline and at the end of study.
Results:Curcumin supplementation significantly elevated serumMDA, SOD activity and TAC level (P<0.001 for all variables) compared with placebo.
Conclusion:The results showed that curcumin supplementation can improve oxidative indices in diabetic patients.
Keywords: Curcumin;Type II diabetes mellitus; Malondialdehde;Total antioxidant capacity;Superoxide dismutase
Biography:
YunesPanahi received his PhD (in Clinical Pharmacotherapy) degrees from the Tehran University of Medical Sciences (Tehran, Iran), and is currently serving as a Professor at the Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. His research focuses on the clinical investigation of natural products.
Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town
Background: Warfarin is the most commonly used drug in the management of thromboembolic disease. However, there is a huge variability in the time, number of doses or starting doses for patients to achieve the required international normalised ratio (INR) which is compounded by a narrow therapeutic index. Many genetic-association studies have reported on European and Asian populations which have led to the designing of specific algorithms that are now being used to assist in warfarin dosing. However, very few or no studies have looked at the pharmacogenetics of warfarin in African populations, yet, huge differences in dosage requirements to reach the same INR have been observed.
Objective: We set out to investigate the distribution of 3 SNPs CYP4F2 c.1347C>T, VKORC1 g.-1639G>A and VKORC1 c.1173C>T among South African Mixed Ancestry (MA) and Black African patients.
Methods: DNA was extracted from 383 participants and subsequently genotyped using PCR/RFLP for the CYP4F2 c.1347 (V433M) (rs2108622), VKORC1 g.-1639 (rs9923231) and VKORC1 c.1173 (rs9934438) SNPs.
Results: Comparing the Black and MA groups, significant differences were observed in the distribution of the following genotypes; CYP4F2 c.1347C/T (23% vs. 39% p=0.03). All VKORC1 g.-1639G>A genotypes (p<0.006) and all VKORC1 c.1173C>T genotypes (p<0.007).
Conclusion: CYP4F2 c.1347T (V433M) reduces CYP4F2 protein levels and therefore expected to affect the amount of warfarin needed to block vitamin k recycling. The VKORC1 g-1639A variant alters transcriptional regulation therefore affecting the function of vitamin k epoxide reductase in vitamin k production. The VKORC1 c.1173T variant reduces the enzyme activity of VKORC1 consequently enhancing the effectiveness of warfarin. These are preliminary results; more genetic characterization is required to understand all the genetic determinants affecting how patients respond to warfarin.
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