Design, Synthesis, Pharmacological and Pharmacoinformatic Analysis of Novel Coumarin-Based Hydrazone Derivatives as Anticancer Drugs

Abstract

Cancer is one of the major causes of death globally after heart disease. To identify potent and selective anticancer drugs with minimum or less side effects is a serious concern and goal of the medicinal chemists. This study focuses on the design, synthesis, pharmacological and pharmacoinformatic evaluation of the novel coumarin-based hydrazone derivatives and accordingly this dissertation is divided into five chapters.
The first chapter briefly highlights the chemical properties and synthesis of the coumarin derivatives in addition to the descriptions about cancer and its treatments. Natural and synthetic coumarin-based hydrazone derivatives reported in the literature as anticancer agents have been categorized according to their structural features and rational approaches.
The second chapter deals with the design, synthesis, biological and cheminformatics evaluation of the coumarin-based hydrazone derivatives. This chapter reports the synthesis of four different types of coumarin-based hydrazones and studies on the evaluation of their anticancer actions in different human cancer cell lines. The tested compounds were compared with doxorubicin as the standard anticancer drug. All the tested compounds exhibited good to moderate cytotoxicity with IC50 values ranging from 6.07 to 60.45 μM in all the tested cancer cell lines. Based on the screening results, it was found out that the compounds, 82a and 84a, showed significant cytotoxicity. In vitro tubulin polymerization inhibition assay was performed for the most potent compounds such as 82a and 84a. These two compounds displayed good potency towards inhibition of tubulin polymerization. The interaction of these compounds with tubulin protein was also studied with the help of molecular docking technique by using discovery studio software. Further, the molecular and ADMET properties were predicted by using Osiris property software and PreADMET server. All the compounds showed promising....