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 H NMR, 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.

Design, synthesis, in silico toxicity prediction, molecular docking, and evaluation of novel pyrazole derivatives as potential antiproliferative agents.

A new series of pyrazole derivatives were designed by docking into vascular endothelial growth factor receptor-2 (VEGFR-2) kinase active site. The designed compounds were synthesized and evaluated for in vitro antiproliferative activity against HT-29 colon and PC-3 prostate cancer cell lines, and angioinhibitory activity in chorioallantoic membrane (CAM) model. Based on the obtained antiproliferative activity results of in vitro and CAM assay, compounds 4b, 4c, 4f, 5b, 5c and 5f were selected, and tested for anticancer activity using in vivo ehrlich ascites carcinoma (EAC) bearing mice.