Targeting VEGFR2 protein by marine Streptomyces globosus VITLGK011-derived compound BECA: An in vitro and in silico analysis.
Lokesh RaviJeyaraman JeyakanthanKrishnan KannabiranPublished in: Journal of basic microbiology (2020)
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.
Keyphrases
- induced apoptosis
- endoplasmic reticulum stress
- protein protein
- vascular endothelial growth factor
- signaling pathway
- oxidative stress
- flow cytometry
- amino acid
- binding protein
- molecular docking
- cell cycle arrest
- drug induced
- squamous cell carcinoma
- cell death
- young adults
- cancer therapy
- single molecule
- electron transfer
- adverse drug
- pi k akt
- data analysis
- crystal structure
- aedes aegypti