Synthesis, cytotoxicity assessment and molecular docking of novel thienyl-pyrazoles as VEGFR2 Inhibitors.

Document Type : Original research articles

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1 Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt

2 Department of Chemistry, Faculty of Science ,Al-Azhar University, Cairo, Egypt.

Abstract

Novel series of thienyl-pyrazole derivatives have been developed and evaluated for antiproliferative efficacy on the basis of researches demonstrating the significance of the pyrazole framework in managing cancer progression and suppression of VEGFR-2. Three cancer cells were used to assess the antitumor efficacy of the new hits, namely; human colon (HCT-116), mammary gland (MCF-7), and prostate (PC-3) cancer cell lines. The cytotoxic screening revealed that breast and prostate tumors are very sensitive to compound 3, displaying superior activity to the reference drug sorafenib. Compound 3 displayed 2.1, 1.2 folds the activity of sorafenib against MCF-7 (IC50=3.36±0.2μM), and PC-3 (IC50=9.58±0.7μM) cell lines, respectively. Furthermore, compound 3 showed 73% of the anticancer activity of the reference drug against HCT-116 (IC50=7.41±0.5μM) cell line. The in vitro anti-VEGFR2 activity of most active derivative 3 was estimated, it revealed good inhibitory efficiency comparing to sorafenib. Furthermore, molecular modeling simulation of the intriguing derivative, was achieved to spotlight its binding interactions and affinity towards the VEGFR-2 active site.

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