New thiosemicarbazones: synthesis, structural characterization, in vitro, and in silico evaluation of antiproliferative effects

新型硫代氨基脲类化合物:合成、结构表征、体外和计算机模拟抗增殖活性评价

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Abstract

AIMS: To design, synthesize, and characterize N-(4-bromophenyl)-2-(substituted fluorobenzylidene)hydrazine-1-carbothioamides (II-IV) and evaluate their in vitro cytotoxicity against DLD-1 and MDA-MB-231 cells, supported by molecular docking. MATERIALS & METHODS: Compounds were obtained by condensations of substituted fluorobenzaldehydes with N-(4-bromophenyl)hydrazinecarbothioamide and characterized by NMR, FTIR, and MS. DLD-1 and MDA-MB-231 cells were exposed to 50-1600 µg/mL for 24 h; viability was measured using a commercial colorimetric assay. Statistics used one-way ANOVA with post hoc tests. Blind docking was performed with CB-Dock2 and interactions inspected in Discovery Studio. RESULTS: All compounds decreased viability in a concentration-dependent manner. In MDA-MB-231, Compounds I, II, and IV showed significant effects (ANOVA p < 0.001). In DLD-1, Compound IV reached p ≤ 0.01 and Compounds I-II p < 0.001; the IC(50) of Compound I in DLD-1 was 1383.2 µg/mL. Docking suggested favorable binding poses stabilized by hydrogen bonding and hydrophobic/halogen interactions at key residues. CONCLUSIONS: The 4-bromophenyl thiosemicarbazone/Schiff-base scaffold exhibits measurable antiproliferative activity with substitution-dependent trends supported by docking. These findings warrant structure optimization to enhance potency and selectivity and motivate follow-up mechanistic assays. (Not a clinical trial; CONSORT not applicable.).

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