Журнал прикладной биоинформатики и вычислительной биологии

Anti-Angiogenic Potential of Secondary Metabolites against Tyrosine Kinase Domain of Vascular Endothelial Growth Factor Receptor-1: An in silico Approach

Upendra N Dwivedi, Aleena Asif, Sameeksha Tiwari, Om Prakash and Veda P Pandey

Angiogenesis, i.e. formation of new blood vessels, is a key hallmark of tumor growth and progression. The tyrosine kinase (TK) domain of vascular endothelial growth factor receptor (TK-VEGFR-1) is reported as the key intracellular domain responsible for the downstream signalling leading to angiogenesis. Therefore, targeting TK domain of VEGFR-1 and blocking downstream signalling is considered as a promising approach in cancer therapy. Furthermore, in view of severe side effects exhibited by present day synthetic drugs, directed against TK domain of VEGFR-1, there is a worldwide effort to identify safer alternatives drugs, especially coming from natural sources. Keeping this perspective in mind, in the present paper, we have evaluated the anti-angiogenic potential of ADMET screened 18 alkaloids, 26 flavonoids and 9 terpenoids against TK domain of VEGFR-1 through molecular docking approach. Results of the analyses revealed that the alkaloid liriodenine (-7.10 Kcal/Mol), flavonoid glabridin (-9.85 Kcal/mol) and terpenoid sarsasapogenin (-9.58 Kcal/mol) were found to be the best among respective classes. However, across the three classes, flavonoid glabridin was found to be the most potent inhibitor. An assessment of anti-angiogenic potential of the flavonoid glabridin with that of FDA approved drug regorafenib revealed comparable results. Results of docking were further validated using molecular dynamics simulation (MDS) analyses. Thus, the present study makes a foundation for further investigations based on the experimental data (wet laboratory data) for therapeutic application of screened secondary metabolites in general and glabridin and sarsasapogenin in particular