Identification of Potent VEGF Inhibitors for the Clinical Treatment of Glioblastoma, A Virtual Screening Approach

Yadav, Mohini; Khandelwal, Ravina; Mudgal, Urvy; Srinitha, Sivaraj; Khandekar, Natasha; Nayarisseri, Anuraj; Vuree, Sugunakar; Singh, Sanjeev Kumar

doi:10.31557/APJCP.2019.20.9.2681

Identification of Potent VEGF Inhibitors for the Clinical Treatment of Glioblastoma, A Virtual Screening Approach

Document Type : Research Articles

Authors

¹ In silico Research Laboratory, Eminent Biosciences, Indore – 452 010, Madhya Pradesh, India.

² Bioinformatics Research Laboratory, LeGene Biosciences Pvt Ltd., Indore-452010, Madhya Pradesh, India.

³ Department of Biotechnology, Lovely Faculty of Technology and Sciences, Division of Research and Development, Lovely Professional University, Phagwara, Punjab-144411, India.

⁴ Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi-630 003, Tamil Nadu, India.

10.31557/APJCP.2019.20.9.2681

Abstract

Vascular endothelial growth factor (VEGF) expression could be found in all glioblastomas. VEGF takes part in numerous changes including the endothelial cell proliferation, the vasculature of solid tumor: its survival invasion, and migration, chemotaxis of bone marrow-derived progenitor cells, vasodilation and vascular permeability. VEGF inhibition can be a smart therapeutic strategy because it is extremely specific and less toxic than cytotoxic therapy. To establish better inhibition of VEGF than the current inhibitors, present study approach is by molecular docking, virtual screening to illustrate the inhibitor with superior affinity against VEGF to have a cautious pharma profile. To retrieve the best established and high-affinity high affinity molecule, Molegro Virtual Docker software was executed. The high-affinity scoring compounds were subjected to further similarity search to retrieve the drugs with similar properties from pubchem database. The completion of virtual screening reveals that PubChem compound SCHEMBL1250485 (PubChem CID: 66965667) has the highest affinity. The study of the drug-likeness was verified using OSIRIS Property Explorer software which supported the virtual screened result. Further ADMET study and drug comparative study strongly prove the superiority of the new established inhibitor with lesser rerank score and toxicity. Overall, the new inhibitor has higher potential to stop the expression of VEGF in glioblastoma and positively can be further analysed through In vitro studies.

Keywords

Main Subjects