Design, synthesis, and evaluation of novel thiadiazole derivatives as potent VEGFR-2 inhibitors: a comprehensive <i>in vitro</i> and <i>in silico</i> study
Ibrahim H. Eissa, Walid E. Elgammal, Hazem A. Mahdy, Susi Zara, Simone Carradori, Dalal Z. Husein, Maymounah N. Alharthi, Ibrahim M. Ibrahim, Eslam B. Elkaeed, Hazem Elkady, Ahmed M. Metwaly
Abstract
OBJECTIVE: analyses. METHODS: )-ylidene)hydrazono) ethyl) phenyl) benzamide) on cell cycle arrest and apoptosis induction. Furthermore, computational investigations, including molecular docking, MD simulations, DFT calculations, MM-GBSA, PCAT, and ADMET predictions were conducted. RESULTS: 0.19 μM). Mechanistic studies revealed its ability to arrest the cell cycle of MCF-7 cells and induce apoptosis (total apoptosis 34.47%, early apoptosis 18.48%, and late apoptosis 15.99%), supported by upregulated caspase-8 (3.42-fold) and caspase-9 (5.44-fold) expression. Additionally, 20b arrested the cell cycle of MCF-7 cells at the %G0-G1 phase. Computational investigations provided insights into its molecular interactions with VEGFR-2, contributing to the rational design and understanding of its pharmacological profile. CONCLUSIONS: Compound 20b presents as a promising anti-proliferative agent targeting VEGFR-2. Also, this comprehensive investigation underscores the potential of 2,3-dihydro-1,3,4-thiadiazole derivatives as promising candidates for further development in anti-cancer research.