Design, synthesis and evaluation of anticancer activity of new pyrazoline derivatives by down-regulation of VEGF: Molecular docking and apoptosis inducing activity

Two series of pyrazoline compounds were designed and synthesized as antipmliferative agents by VEGFR pathway inhibition. All synthesized compounds were screened by the National Cancer Institute (NCI), Bethesda, USA for anticancer activity against 60 human cancer cell lines. Compound 3f exhibited the highest anticancer activity on the ovarian cell line (OVCAR-4) with IC50 = 0.29 mu M and on the breast cell line (MDA-MB-468) with IC50 = 0.35 mu M. It also exhibited the highest selectivity index (SI = 74). Compound 3f caused cell cycle arrest in OVCAR-4 cell line at the S phase which consequently inhibited cell proliferation and induced apoptosis. Moreover, 3f showed potent down-regulation of VEGF and p-VEGFR-2. Docking studies showed that compound 3f interacts in a similar pattern to axitinib on the VEGFR-2 receptor. The same compound was also able to fit into the gorge of STAT3 binding site, the transcription factor for VEGF, which explains the VEGF down-regulation.

Automated summary

Two series of pyrazoline compounds were synthesized as antiproliferative agents targeting the VEGFR pathway. Compound 3f showed the highest anticancer activity against ovarian and breast cancer cell lines, inhibiting cell proliferation and inducing apoptosis. It also down-regulated the expression of VEGF and p-VEGFR-2. Docking studies revealed its similar interaction pattern to axitinib on VEGFR-2 receptor and its ability to fit into the STAT3 binding site, explaining the down-regulation of VEGF.