Human DHFR inhibitors: From in silico to novel leads

5^th International Conference on Medicinal Chemistry & Computer Aided Drug Designing and Drug Delivery

December 05-07, 2016 Phoenix, USA

Amit G Nerkar

Savitribai Phule Pune University, India

Posters & Accepted Abstracts: Med chem

Abstract :

Background & Aim: Human dihydrofolate reductase is the pivotal enzyme received much attention with its gold standard inhibitor methotrexate. With this inspiration, the research was aimed to design and synthesize dihydrofolate reductase inhibitors (DHFR) for anti-cancer activity. Methods: In silico screening of some Quinazolines by Vlife MDS 4.2 software, their synthesis in vitro and in vivo pharmacological screening were performed to obtain quinazoline leads for hDHFR inhibition. Structure of the ligands were drawn by Marvinsketch to convert 2D molecules to Mol file followed by optimization of ligands by energy minimization and was carried by molecular mechanics force field (MMFF) on V-Life MDS 4.2 software. Lastly Docking was done and docking scores were compared with standard drug Methotrexate for prioritization of molecules. Further these prioritized molecules were synthesized. The reactions were monitored by TLC and synthesized molecules were characterized IR and NMR spectroscopy. At the end the molecules were evaluated for in vitro anticancer assay on ten different cell lines as per National Cancer Institute, Bethesda guidelines, followed by in vivo assay. Results & Conclusion: Molecules showed comparable inhibition both in in-silico and in-vitro assays to that of Methothrexate taken as standard.

Biography :

Email: amit.nerkar@sinhgad.edu