Exploration of Anticancer Potential of Spiropyranopyrazole Derivatives as CDK7 Inhibitors

Abstract

Purpose : The Spiropyranopyrazole derivatives are used as cytotoxic agents and nitrogen containing heterocyclic analogs targeting CDK7 inhibition shows better cytotoxic activity. Methodology : A new series of compounds were synthesized using various substituted isatin derivatives and then characterized and analyzed for biological activity by in-silico and using MTT assay targeting CDK7. All the synthesized compounds were analyzed for their biological activity for this purpose breast cancer cell lines (MCF7) were used and analyzed by MTT assay. Docking studies into ATP binding site of CDK7 were performed to predict their binding affinity scores and possible interactions with receptor to evaluate bioactivity in-silico using VLife MDS 4.3. Findings : A novel series of Spiropyranopyrazole derivatives were successfully synthesized via Multicomponent reaction (MCR). From experimental data indicated that compounds 2c and 3c showed most promising results as their inhibitory activity with 23.20% and 26.50% respectively at 10μM and these were selected for further preclinical studies. Social Implications : If the present findings of spiropyranopyrazole derivatives passes preclinical studies and we develop drug like candidate then it is a massive achievement in anticancer therapy that could save many lives. Original : Successfully develop a novel series of spiropyranopyrazole having CDK7 inhibitor activity. This could be helpful for development of a drug like candidate having significant cytotoxic activity.