MOLECULAR DOCKING AND INTERACTION OF COUMARIN DERIVATIVES AS INHIBITORS OF GROWTH FACTOR RECEPTORS

Abstract

Objective: Cancer is the largest cause of mortality in the globe, accounting for over 10 million deaths in 2020, or roughly one in every six. Because growth factor receptors are involved in the pathophysiology of the disease in several ways, human epidermal growth factors (HER-2 and HER-3) and vascular endothelial growth factor receptors (VEGFR-2 and VEGFR-3) might be as considered therapeutic targets. Coumarins and derivatives were chosen for this study to investigate their pharmacological characteristics and therapeutic effect against the targeted proteins implicated in the pathogenesis of different cancers. Methods: In this work, 50 coumarins and their derivatives were chosen to assess their binding affinity with the targeted proteins (HER-2, HER-3, VEGFR-2, and VEGFR-3). PyRx, a virtual tool, was utilized to perform molecular docking. The investigation was carried out computationally, with data and molecular structures of the phytocompounds and proteins derived from Indian medicinal plants, phytochemistry, and therapeutics, as well as PubChem. The protein structure was validated using a variety of tools, including Protein Data Bank sum generate and BIOVIA discovery studio software. The pharmacological assessment of the ligands was carried out using ADMET filters. Results: According to the results of molecular docking, the ligands Glycycoumarin, Mutisifurocoumarin, Thunberginol A, Pervilleanine, Licocoumarin A, and Murrayacoumarin C had the lowest binding affinity toward the four targeted proteins. Conclusion: Since these compounds are effective against the growth factor receptors implicated in cancer pathogenesis, they could be a suitable candidate for cancer management and suppression. However, in vitro research is still required to support these findings.