Design, synthesis, in silico and antiproliferative evaluation of novel pyrazole derivatives as VEGFR-2 inhibitors.

As the blockade of the VEGFR-2 signaling pathway is a viable approach in cancer therapy, the present study focuses on a series of pyrazole based VEGFR-2 inhibitors that were designed on the basis of the hybridization approach, supported by docking and in silico computational studies. The designed compounds were synthesized through facile synthetic methods and the structures were confirmed by 1 H NMR, 13 C NMR, MS and elemental analysis. The compounds were screened for in vitro antiproliferative activity against the HT-29 (human colon cancer) and MCF-7 (human breast cancer) cell lines by MTT assay. The compounds were also studied for in vitro inhibitory activity against VEGFR-2 kinase. Among all the tested compounds, compound 6h emerged as a potent agent in the antiproliferative study against HT-29 and MCF-7 cells, with IC50 values of 2.36 and 6.59 μM, respectively. Moreover, the same compound exhibited the highest VEGFR-2 inhibitory activity with an IC50 value of 1.89 μM. In docking studies, the designed compounds showed similar and essential key interactions as those of known VEGFR-2 inhibitors. The present study may lead to new molecules in the development of anticancer agents targeting VEGFR-2.