Design, synthesis, and biological evaluation of sulfonamide-functionalized pyridine carbothioamides as potent tubulin-targeting anticancer agents.

ABSTRACT: Pyridine carbothioamides (PCAs) are recognized for their gastric mucosal protective effects and low in vivo toxicity, making them attractive scaffolds for anticancer drug development. In this study, a series of N-phenyl 4-substituted and 2,4-disubstituted PCAs (1-8) incorporating a sulfonamide pharmacophore were synthesized, fully characterized, and evaluated as tubulin polymerization inhibitors. The compounds were tested against four cancer cell lines (A549, MCF-7, PC-3, HepG2) with colchicine and doxorubicin as reference drugs. Among them, compounds 3 and 5 exhibited potent cytotoxicity, being 2-6-fold more active than colchicine and up to 2.5-fold stronger than doxorubicin in PC-3 cells. Importantly, both showed ∼4-fold lower toxicity toward normal HLMEC cells and displaye

SUBMITTER: Younas F 

PROVIDER: S-EPMC12624752 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature