Anti-angiogenic potential of bioactive phytochemicals from Helicteres isora targeting VEGFR-2 to fight cancer through molecular docking and molecular dynamics simulation

Abstract

Cancer is one of the leading causes of death due to its very high rate of morbidity and mortality, and there is a constant demand of effective drugs for cancer therapy. Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a significant role as central modulator of angiogenesis and is targeted frequently for developing anti-angiogenic agents to fight cancer. Helicteres isora L. (Malvaceae) is reported to possess diverse medicinal properties including anti-cancer potentials. In the current investigation, 38 bioactive phytochemicals of H. isora were screened virtually to evaluate their anti-angiogenic potentials targeting VEGFR-2. The study unveiled three potential candidates such as, Diosgenin (-9.8 Kcal//mol), Trifolin (-8.4 Kcal/mol) and Yohimbine (-8.1 Kcal/mol) that showed favorable pharmacokinetic, pharmacodynamic and toxicity properties with no significant side effects. Molecular dynamics simulation employing 100ns revealed noteworthy structural stability and compactness for all the top three candidates. The MM/GBSA binding free energy estimation corroborated the docking interactions where Yohimbine (-30.47 Kcal/mol) scored better than Diosgenin (-27.54 Kcal/mol) and Trifolin (-29.58 Kcal/mol). Target class prediction revealed enzymes in most of the cases and some FDA approved drugs were found as structurally similar analogs for Trifolin and Yohimbine. These findings could lead to the development of novel and effective anti-angiogenic agents. Communicated by Ramaswamy H. Sarma.