Design and synthesis of VEGFR-2 tyrosine kinase inhibitors as potential anticancer agents by virtual based screeningt

作者：Patel Harun M; Bari Pankaj; Karpoormath Rajshekhar; Noolvi Malleshappa; Thapliyal Neeta; Surana Sanjay; Jain Pritam^*

来源：RSC Advances, 2015, 5(70): 56724-56771.

DOI：10.1039/c5ra05277g

Vascular endotheLiaL growth factor receptor-2 (VEGFR-2) Ways a cruciaL roLe in cancer angiogenesis. A Library of 6,7-dimethoxy quinazoLine was prepared using a Ligand based drug design approach and passed through different lifters of virtuaL screening such as a docking study and Lipinski's ruEe. Twenty virtuaLLy screened compounds were synthesized and investigated against VEGFR-2 kinase and human umbiLicaL vein endotheLiaL ceLLs (HUVEC) in vitro. VirtuaLLy screened compound 47 having 4chLorophenyL-1,3,4-thiadiazoLe substitution at 3rd position of 6,7-dimethoxy-2-phenyLquinazoLin-4(3H)-one exhibited the most promising activity, with IC50 vaLues of 3.8 nm and 5.5 nm against VEGFR-2 tyrosine kinase and the HUVEC ceLL Line. Docking simuLation supported the initiaL pharmacophoric hypothesis and suggested a common mode of interaction at the ATP-binding site of VEGFR-2 demonstrating that compound 47 is a potentiaL agent for cancer therapy that deserves further research.

• 出版日期2015