Carbothioamide Derivatives as Potent Inducers of Schizosaccharomyces Pombe Cytotoxicity: Synthesis, Characterization, and Pharmacological Evaluation

Abstract A novel series of (E)-2-[(E)-3-(2-butyl-4-chloro-1H-imidazol-5-yl)-1-phenylprop-2-en-1-ylidene]hydrazine-1-carbothioamide derivatives 5a–5e were synthesized by the condensation of imidazole-substituted chalcones 3a–3e with hydrazinecarbothioamide (4) using glacial acetic acid as a catalyst under reflux conditions. Imidazole-substituted chalcones 3a–3e were prepared by the condensation of 2-butyl-4-chloro-1H-imidazole-5-carbaldehyde (1) with substituted acetophenones 2a–2e under basic conditions via the Claisen–Schmidt reaction. All synthesized carbothioamide derivatives 5a–5e were characterized by various spectroscopic techniques, including FT-IR, UV-Vis, 1H NMR, and mass spectrometry and by elemental analysis. Their in vitro cellular-level cytotoxicity against Schizosaccharomyces pombe cells was evaluated, and the percentage viability was observed to be in the range of 75–100%. A minimum inhibitory concentration (MIC) assay was performed to determine the antibacterial potency of carbothioamide derivatives 5a–5e against Salmonella typhimurium, Escherichia coli, Bacillus megaterium, and Staphylococcus aureus. The MIC values of the synthesized compounds ranged from 11 to 25 μg/mL, demonstrating remarkable antibacterial activity against all tested bacterial strains, comparable to that of the standard drug ciprofloxacin. In addition, the antifungal activities of compounds 5a–5e against Aspergillus niger were observed with MIC values of 17–25 µg/mL. Furthermore, a molecular docking study of the compounds was performed against human topoisomerase II alpha in complex with DNA and etoposide (PDB ID: 5GWK), with observed binding energies ranging from –9.3 to –10.5 kcal/mol. The synthesized derivatives demonstrated distinctive binding affinities and modes. ADME properties were calculated for all carbothioamide derivatives 5a–5e, and the results suggest that the compounds possess favorable properties for oral activity.