Targeting VEGFR2 protein by marine Streptomyces globosus VITLGK011-derived compound BECA: An in vitro and in silico analysis

Abstract

This study investigates the anticancer cytotoxic mechanism of action of benzoyloxy-ethyl-carbamic acid (BECA) produced by Streptomyces globosus VITLGK011. Flow cytometry analysis confirmed that BECA (at IC₅₀ : 3.12 µg/ml) treatment for 24 h induced apoptosis in 60% of cells. Schrodinger Maestro tools such as QikProp and DFT were used to confirm that BECA is an eligible drug-like molecule, with suitable physiochemical properties. Glide XP tool was used to perform induced-fit docking between BECA and 30 cancer drug target proteins. The highest significance was observed for VEGFR2 protein (-6.7 kcal/mol). GROMACS tool was used to perform molecular dynamic simulation between BECA and VEGFR2 protein for 40 ns. Root mean square deviation, root mean square fluctuation, H-bond, and trajectory analysis, confirmed that BECA is a suitable inhibitor of VEGFR2 protein. Results conclude that BECA is a valid VEGFR2 inhibitor, and it thus exerts the observed anticancer cytotoxicity against MCF-7 cells.

Keywords: GROMACS; Glide XP; Schrodinger Maestro; benzoyloxy-ethyl-carbamic acid; density functional theory.