Modern day medicinal chemistry demands discovery of novel molecules to overcome the drawbacks of existing drugs providing better therapeutic effects. In this regard, synthetic drugs, natural and marine products have inspired medicinal chemists to tune the molecular structure of compounds with relevant modifications for the discovery of a new chemical entity. Structure based drug designing and scaffold hopping has led to discovery of new potential compounds with inclusion of important pharmacophoric features of the already established drugs. Merbarone is a clinical trial agent which was found to be htopoIIα inhibitor. Merbarone and the molecules already reported as topoiomerase II inhibitors prompted us to design and synthesize scaffold hopped analogs of merbarone. Versatile derivatives of pyrimidine-triones (Series 1) and their furo-fused derivatives (Series 2) with relevant biological substitutions/functionalities were synthesized. All the synthesized compounds were subjected to topoisomerase II inhibitory and antiproliferative bio-evaluation studies. htopoIIα inhibitory activity was performed using decatenation and some of the compounds were found to be active as compared to the standard drug Etoposide (an anticancer drug that inhibit hTopoIIα). Cell line studies for anti-proliferative and anti-migratory studies are underway. The mechanism for the inhibition of the cell cycle of the topoisomerase is also under plan. Synthesis and bioactivity results including anti-proliferative and Topo-II inhibitory activity, mechanism of inhibition as a comprehensive scaffold hoping strategy will be presented in the meet.

Clinical trial agent inspired strategy: Discovery of scaffold hopped analogs of Merbarone hTopoIIα inhibitors

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.