Xanthones from Garcinia genus as potential Human vascular endothelial growth factor receptor 2 (kdr) kinase domain inhibitors: An In silico analysis
Sandeep Kumar Jain R., Meghana P., Prashanth N., Sandeep Telkar, and Kumaraswamy H. M.*
Laboratory of Experimental Medicine, Department of Biotechnology, Kuvempu University, Shankaraghatta-577 451 (India) *Corresponding Author Address: Dr. Kumaraswamy H M, Department of Biotechnology, Kuvempu University, Shankaraghatta-577 451 (India) E-mail: drhmklab@gmail.com
ABSTRACT
Vascular endothelial growth factor (VEGF) is an important signaling protein involved in angiogenesis and vasculogenesis. VEGF binding to tyrosine kinase receptors (VEGFR) can cause itself dimerization and become turn on through transphosphorylation. There are three main subtypes of VEGFR: VEGFR1, VEGFR2, and VEGFR3. VEGFR2 appears to be involved in virtually all of the known cellular responses to VEGF.Blocking the angiogenesis process of solid tumours by inhibiting the tyrosine kinase VEGFR2 signalling pathway could stop tumour growth and spread.As a result, designing inhibitors that target VEGFR2 is a promising strategy for developing new therapeutics. Xanthones are well recognized as chemotaxonomic markers for Garcinia genus. Many xanthones have been reported for several pharmacological properties. In the present study insilico analysis is used to assess the potentiality of xanthones as VEGFR2 inhibitors. Structures of ten different xanthones were retrieved from pubchem. Preliminary screening of compounds was done in accordancewith Lipinski’s rule of five. A docking simulation was carried out using a predictive docking tool Autodock Vina to obtain model structures of VEGFR2- xanthones complex. Xanthones and standard drug ‘AAL993’ showed no violation of ‘Lipinski’s rule of five’ except ‘Garcinone c’ with only one violation. The binding energies of all compounds ranged from -7.2 to -8.3 Kcal/mol and standard drug ‘AAL993’ showed -11.3kcal/mol binding energy with two or more hydrogen bonds. To confirm the in silico findings, further preclinical and clinical research is required.