Design, synthesis, and anticancer evaluation of novel pyrazole-thiophene hybrid derivatives as multitarget inhibitors of wild EGFR, mutant (T790M) EGFR, and VEGFR-2.

ABSTRACT: A new series of pyrazole-thiophene hybrid derivatives was rationally designed, synthesized, and biologically evaluated for anticancer potential. Cytotoxicity screening toward MCF-7 and HepG2 cell lines identified 2 as the most potent analogue (IC₅₀ = 6.57 μM, MCF-7; 8.86 μM, HepG2), with activity comparable to the reference drugs doxorubicin, erlotinib, and sorafenib. Selectivity toward MCF-7 was observed for 8 (IC₅₀ = 8.08 μM), while 14 displayed moderate dual activity (IC₅₀ = 12.94 μM, MCF-7; 19.59 μM, HepG2). Enzyme inhibition assays revealed that 2 effectively suppressed wild-type EGFR (IC₅₀ = 16.25 μg mL^-1) and the clinically relevant T790M mutant (17.8 μg mL^-1), whereas 14 showed balanced dual inhibition (16.33 and 16.

SUBMITTER: Sallam MN 

PROVIDER: S-EPMC12541710 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature