Day :
- Pharmaceutical Research & Development
Session Introduction
Arjim G. Luna
National University, Manila
Title: Analgesic Potential of Kauayan – Tinik (Bambusa Spinosa Roxb.) Leaves Ethanolic Extractive
Biography:
Arjim G. Luna graduated cumlaude from the Colegio de San Gabriel Arcangel with the degree of BS in Pharmacy in April 2014 and passed the PLE on the same year. He is currently finishing his MS degree in Pharmacy (Industrial Pharmacy) at University of the Philippines Manila. He is an Assistant Professor II at National University, Philippines, and as lecturer at Spearhead Capitol Review Center. He handles professional courses such as Manufacturing Pharmacy, Drug Delivery Systems, Microbiology and Parasitology, Pharmacognosy with Plant Chemistry and Pharmaceutical Chemistry. He is also an area coordinator of Young Pharmacists Group Bulacan Chapter, member of scholastic publications and other professional organizaions.
Abstract:
Substances from plants have recently become of great interest of owing to their versatile applications. As for the continuous use of herbal remedy, the researchers want to open the minds of people that they can use herbal medicines as an alternative for synthetic medicines. One of the medicinal plants that can be found in this country is the Kauayan - tinik (Bambusa spinosa Roxb.) or the spiny bamboo. Though abundantly found and easily grown botanical, there is no known attempt yet use the study of the analgesic property of the plant. The method of research was employed is experimental. The laboratory experimentation that consists the major portion of the investigation was the following: (1) Collection and extraction of plant sample; (2) Phytochemical screening; (3) Physical evaluation; (4) Instrumental analysis using the Fourier Transform Infrared Spectroscopy (FTIR); and (5) Biological test of analgesic property of ethanolic extract. The Phytochemical screening conducted an eighty percent ethanolic extractives of the Kauayan-tinik leaves gave a positive result for flavonoids, phytosterol, saponins, and proteins. The leaves of Kauayan – tinik extract and extractives gave the negative result for alkaloids, tannin, reducing sugar, and starch. The FTIR scan of the sample was obtained using an attenuated total reflectance (ATR) accessory. Final spectrum was processed using ATR correction. The spectrum yielded the following functional groups: O-H, C-H-O, C-O-O-H, C=O, C=C, N-H, -NO2, C-O-C, S-O and R-X. The analgesic potential of Kauayan – tinik leaves ethanolic extractives was investigated using acetic acid-induced pain test. Isolated extractives were prepared into two different concentrations, the 300 mg/kg and the 600 mg/kg. The 300 mg/kg concentration was found to exhibit 22.22% protection. The 600 mg/kg concentration was found to exert 33.33% protection. Based on the results of the physical and instrumental methods of analysis, the ethanolic extracts and extractives possessed the characteristics features of dark green colored paste and possessed a distinct odor. Base on the results of the acetic acid-induced pain test, the extractives of the leaves of Kauayan - tinik possess analgesic activity.
Nishanth.R, Kaushik Chanda
Department of chemistry, Vellore Institute of Technology, India.
Title: An Expeditious Green Synthetic Design to Access Low Molecular Weight Novel Hybrid Bifunctional Molecules as Anti-Microbials
Biography:
Nishanth.R has completed his M.Pharmacy pharmaceutical chemistry at the age of 25 years from Manipal University.After completion of masters i have worked as a Project assistant at Dr.Reddys Institute of life sciences,India.There i worked on synthesis of Nitrogen,oxygen,carbon containing heterocycles and evaluation of their anti-tubercular activity.Currently i am persuing Ph.D. in Vellore Institute of Technology at Vellore in India.I have published 3 papers in reputed journals.
Abstract:
Antibiotic resistance is a threatening issue being faced by the world today.It is an intrinsic part of bacterial evolution whose genetic basis arise via, chromosomal mutation of bacteria or by the acquisition of resistance genes from other bacteria by horizontal gene transfer [HGT] and by production of β-lactamase. To some extent, bifunctional and hybrid antimicrobials are considered to be the successful outcome of research towards bacterial resistance.MCB-3861 is one such example of fluoroquinolone-oxazolidinone hybrid anti-microbial with a 4-hydroxy piperidinyl linker. It shows resistance against several clinically relevant gram-positive pathogens, including Vancomycin-Resistant Enterococci (VRE), E. faecalis S. pneumonia. Considering an amide in a general view resonance on nitrogen atom attains planar structure with sp2 hybridization which gives best overlap of orbitals with the adjacent carbonyl carbon atom making it less electrophilic and less reactive. Contrarily extensive literature survey on SAR of the lactam containing antimicrobials reveals that, 4-5 ring system in penicillin prevents nitrogen atom in lactam ring from attaining sp2 hybridization. In addition actual ideal bond angle (109.5°) of the sp3 hybridized carbon atom in lactam ring is constricted to 90° leading to angle strain making it susceptible to degradation by βlactamase. From our preliminary work, we found that imidazo [1,2-a]pyridine/pyrimidine/pyrazine derivatives with methyl and methoxy substitutions would be active against gram positive and gram negative bacteria. In this context we underpinned a design to synthesize hybrid antimicrobials by inception of thiazetidine/oxazetidine and thiazolidine/oxazolidine moieties to methyl or methoxy substituted imidazo/ thiazo pyridine/ pyrimidine/pyrazine derivatives which could make a way in discovery of novel hybrid antimicrobials.
Mohua Das
National University of Singapore, Singapore
Title: Multi-protein Dynamic Combinatorial Chemistry: A Novel Strategy of Drug Design
Biography:
Mohua had started her research career with a Masters in Natural Product Chemistry from the National Insitute of Pharmaceutical Education and Research (NIPER, India). The dissertation work in Masters led to her first publication in a peer-reviewed journal Organic Letters, in 2015. She has also received the University Gold Medal for being the best student of the batch in the same year. She is currently pursuing her PhD from the National University of Singapore and already published her first-author paper within three years of her PhD journey.
Abstract:
Dynamic combinatorial chemistry (DCC) is a powerful supramolecular approach for discovering ligands for biomolecules. It is currently of tremendous chemical and biological interest. To date, most, if not all, biologically-templated DCC employ only a single biomolecule in directing the selfassembly process, which severely limits the scope and potential of DCC. Herein, we explored the concept of multi-protein DCC, where two or more target proteins could be used concurrently in the same dynamic system. We envisaged that this will greatly multiply the power and efficiency of DCC. However, such a multi-protein system is extremely challenging to analyse, in part due to the constantly changing nature of dynamic self-assembly. Consequently, to date, there is no report of method suitable for studying multiprotein templated DCC. To overcome this challenge, we developed a novel multi-protein detection strategy which combines the discriminatory power of zwitterionic ‘thermal tag’ with the sensitivity of differential scanning fluorimetry. This strategy is also remarkably sensitive and could differentiate the binding of ligands to different proteins, including structurally-similar subfamily members, which are otherwise challenging to discriminate.When used in combination with DCC, we were able to achieve simultaneous evolution of ligands against several proteins. This led to the concurrent discovery of subfamily-selective probes against two clinically-important epigenetic enzymes, FTO and ALKBH3. To our knowledge, this study represents not only the first report of multi-protein DSF assay, but also a new strategy for probing dynamic chemical system, which hopefully will further our understanding of self-assembly dynamics, and inspire new applications for DCC-based approaches.
Kunal Nepali
Assistant Professor, Taipei Medical university, Taipei, Taiwan
Title: Indole based HDAC6 inhibitors exerting potent antiproliferative effects on colon cancer cells
Biography:
Kunal Nepali is a medicinal chemist working in the field of cancer drug discovery since 2008. He obtained his Ph.D degree in Pharmaceutical Chemistry in the year 2012 from ISF College of Pharmacy, Moga, Punjab, India and is currently working as an Assistant Professor, School of Pharmacy, Taipei Medical university, Taiwan. Prior to this, he was a Post-Doctoral Fellow in the Department of Medicinal Chemistry of the same university. He has been a recipient of outstanding Post-Doctoral Researcher award for the five consecutive years (2014 – 2018) and his scientific interests are centered at the design and synthesis of novel molecular entities as future therapeutics to address the pharmacological problems.
Abstract:
Histone deacetylase 6 (HDAC6) has been recognized as a promising target for tumorigenesis. A selective HDAC6 inhibitor, Tubastatin posseses tetrahydrocarbolines as the CAP construct and has been a subject of extensive structural engineering. Several alterations have been made in its chemical architecture to furnish selective HDAC 6 inhibitors inducing potent antiproliferative effects. Recently, a series of selective HDAC6 inhibitors were designed by our research group employing a ring opening strategy of tetrahydro-γ-carbolines in tubastatin A to generate diverse indole based constructs. The aim of the study was to evaluate the influence of diverse combinations of CAP constructs and linkers bearing the N1-zinc binding domain on the cellular and enzymatic activity. The synthesized compounds were evaluated for in-vitro antiproliferative effects against a panel of human cancer cell lines. The results of the study revealed interesting insights regarding the dependence of activity profile of the compounds on the subtle structural variations. It was found that some selected compounds displayed selective HDAC6 activity comparable to that of tubastatin A. Moroever, significant cell killing effects against HCT116 cells with GI50 ranging from 0.50 – 0.54 µM were also demonstrated by some compounds. The synthetics activated the apoptosis pathway and induced irreversible growth arrest capacities by suppressing colony formation ability. To add on, an upregulation effect on acetyl-tubulin, without significant induction of acetyl-histone H3 was observed by western blot analysis. Overall, the findings of the study are highly promising and the potent compounds identified could emerge as a potential leads for further investigation to develop potent anticancer agents for colon cancer.