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Biography

Mrinal is a Medicinal Chemist and carries thirteen years of experience in small molecule therapeutics via orthosteric/allosteric modulation of GPCR, ion channels and enzymes with a track record in delivering pre-clinical candidates for metabolic disorders, pain, oncology and anti-infective programs. He completed his MS and PhD from internationally reputed Indian Institute of Technology in Bio-organic Chemistry and was awarded Post Doctoral Fellowships in the field of Chemical Biology from University of Uppsala, Sweden, National Institute on Aging in collaboration with The Johns Hopkins University, USA and University of Basel, Switzerland. He is a coauthor
and con-inventor of 10 patents, 15 articles and 1 book chapter.

 

Abstract

Cancer is a disease in which cells divide uncontrollably with the potential to invade or spread to other parts of the body. Over 100 cancers affect human and ~14 million new cases of cancer occurred globally in 2012 resulting ~15% of deaths. Towards our aim in improving the quality of life for the patients suffering from cancer, we are working on two approaches: 1] DNA has played a key role as molecular target in cancer therapeutics. Compounds that target DNA are some of the most effective agents in clinical use and increased in
cancer patients’ survival. Due to their severe toxicity, however, there has been considerable excitement in targeting unusual, non-canonical structures of DNA. In that regard, G-quadruplex structures have drawn interest for studying their potential involvement to inhibit cancer growth and a compound Quarfloxin has even been reached Ph2 clinical trial. 2] On the hand, protein-protein interaction [PPI] is of importance in the regulation of cellular processes and is consequently implicated in the development of various disease states including cancer. The interaction between protein molecules, through Van-der Waals force, Hbonding interaction etc., leads to the formation of a larger
protein complexes performing a specific function. Recently, it is demonstrated, certain classes of PPI can help medicinal chemists to develop inhibitors, and the first PPI inhibitor has entered in clinical development. The presentation will focus on modeling, design, synthesis of novel small molecules and their biological evaluation either as G-quadruplex stabilizing agents or PPI inhibitors. Efficiency of the synthetic compounds was performed to assess the G-quadruplex binding affinity using different biophysical studies. For the PPI inhibitors, potential cell growth inhibition was tested against different cancer cell lines followed by dose response studies. Finally, all the selected compounds were evaluated for liver microsomal stability, aqueous solubility, CYP inhibition studies for druglikeness.