Design and synthesis of thiadiazoles as anticancer, apoptotic, and VEGFR-2 inhibitors

Future Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 1 - 13

Опубликована: Апрель 8, 2025

Vascular endothelial growth factor receptor (VEGFR-2) inhibitors are critical in cancer therapy due to their role suppressing tumor angiogenesis. Herein, we report a new series of thiadiazole-based derivatives as potential VEGFR-2 with promising anticancer activity. The synthesized compounds were evaluated for anti-proliferative activity against human cell lines (HCT-116, MCF-7, and HepG-2), WI-38 normal cells. Sorafenib was used reference drug. inhibitory determined, followed by cycle analysis, apoptosis assays, Q-RT-PCR wound-healing assays. In silico molecular docking conducted explore binding interactions. Among the tested compounds, 13b exhibited potent (IC50: 3.98-11.81 µM) strong inhibition 41.51 nM), surpassing sorafenib 53.32 nM). Cell analysis revealed that induced G2/M phase arrest MCF-7 Apoptosis levels increased from 2% 52%, accompanied > 12-fold rise Bax/Bcl-2 ratio activation caspase-8/9. Additionally, significantly suppressed migration, only 5.28% wound closure. studies confirmed its Thiadiazole-based derivatives, particularly compound 13b, exhibit inhibition, effects, induction, anti-migratory activity, supporting agents.

Язык: Английский

Design, synthesis, in vitro, and in silico studies of new thiadiazol derivatives as promising VEGFR-2 inhibitors and apoptosis inducers

Journal of Molecular Structure, Год журнала: 2024, Номер 1316, С. 139019 - 139019

Опубликована: Июнь 19, 2024

Язык: Английский