A novel sulfamoylphenyl-dihydro-thiadiazole derivative as a dual EGFR and carbonic anhydrase inhibitor for cancer therapy.

ABSTRACT: A novel sulfamoylphenyl-dihydro-thiadiazole derivative (compound 14) has been designed and synthesized as a dual inhibitor targeting EGFR and human carbonic anhydrases (hCA_IX and hCA_XII). Computational studies, including density functional theory (DFT), molecular docking, and molecular dynamics simulations, confirmed its stability, favorable binding interactions, and reactivity profiles. Compound 14 showed potent inhibition of EGFR (IC₅₀ = 10.12 ± 0.29 nM), hCA_IX and hCA_XII (IC₅₀ = 79 ± 1.2 nM and 58 ± 0.9 nM, respectively). Cytotoxicity assays demonstrated selective activity against cancer cells, with IC₅₀ values of 16.13 µM in MDA-MB-231 and 22.57 µM in MCF-7 cells, compared to 148.32 µM in non-cancerous Vero cells. Compared to acetazolamide, compound 14 exhibited improved selectivit

SUBMITTER: Eissa IH 

PROVIDER: S-EPMC12410758 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature