Synthesis, cytotoxicity assessment and molecular docking of novel thienyl-pyrazoles as VEGFR2 Inhibitors. | ||
| Azhar International Journal of Pharmaceutical and Medical Sciences | ||
| Volume 4, Issue 2, June 2024, Pages 33-42 PDF (751.71 K) | ||
| Document Type: Original research articles | ||
| DOI: 10.21608/aijpms.2024.220640.1222 | ||
| Authors | ||
| Lamia HT Amin* 1; Rehab Sabour1; Yossry A Ammar2; Hend MA El-Sehrawi1 | ||
| 1Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt | ||
| 2Department 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. | ||
| Keywords | ||
| thiophene-pyrazole; antitumor; MTT; VEGFR-2; modeling simulation | ||
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