Synthesis, Characterization, and Anticancer Evaluation of Thiourea Benzamide Derivatives and their Cu(II) and Pt(IV) Complexes Against PC3 and HepG2 Cancer Cell Lines
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Abstract
Thiourea derivatives have attracted attention for their pharmaceutical potential due to their diverse biological activities, including anticancer properties against various cancer types. The present study focused on the synthesis, characterization, and anticancer evaluation of thiourea benzamide derivatives and their Cu(II) and Pt(IV) complexes against human prostate cancer (PC3) and human liver cancer (HepG2) cell lines. Two thiourea benzamide ligands, N-([4-chlorophenyl]carbamothioyl)-4-fluorobenzamide (L1) and N-([4-chlorophenyl]carbamothioyl)-4-methoxybenzamide (L2) were synthesized through nucleophilic substitution reactions. Their corresponding copper and platinum complexes were also prepared and characterized. In vitro cytotoxicity was evaluated against PC3 and HepG2 cancer cell lines using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Molecular docking studies were performed to assess binding affinities to cancer-related proteins. Computational analyses, using density functional theory (DFT) were conducted to provide theoretical insights into the geometrical structures. The synthesis of thiourea benzamide derivatives and their Cu(II) and Pt(IV) complexes resulted in several structurally characterized compounds with distinct spectral properties. Anticancer evaluations revealed that the Cu-based complex ([Cu(L2)₂].2H₂O) exhibited moderate activity against PC3 and HepG2 cell lines and the Pt-based complex ([Pt(L2)₂Cl₂].H₂O) demonstrated significantly lower efficacy against PC3 but showed promising effects against HepG2. Molecular docking indicated stronger interactions of the Pt complex with target proteins, highlighting its potential as a more effective inhibitor than the ligands and Cu complex. These findings underscore the therapeutic potential of thiourea derivatives and their metal complexes in anticancer drug development, suggesting further exploration into their mechanism of action and application in targeted therapies.
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