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Carbothioamides as anticancer agents: synthesis, in-vitro activity, structure-activity relationship evaluations and molecular docking

Year: 2025

Type: article

Abstract: Carbothioamides exhibit many biological properties, including antiviral, antibacterial and anticancer activities. Their ability to interfere with DNA synthesis is mainly responsible for their anticancer activities. Here, twelve phenyl-substituted carbothioamides ( 2−13 ) were synthesized and characterized using Electron Ionization Mass Spectrometry (EI-MS), proton and carbon-13 nuclear magnetic resonance (HNMR, and 13 C NMR), Infrared (IR), and elemental analysis. The anticancer activity of the carbothioamide derivatives ( 2–13 ) was measured in the HCT116 colorectal cancer cell line by means of a three day sulforhodamine B (SRB) proliferation assay. Among the series, four compounds ( 2 , 4 , 11 , and 12 ) which inhibited the cell viability by more than 50 % at 50 μM concentration. IC 50 determination of these four compounds revealed 1-benzoyl-4-(2-bromophenyl) thiosemicarbazide ( 11 ) as the most potent compound with IC 50 values of 21.61 ± 4.77 μM, 18.34 ± 3.53 μM and 17.87 ± 12.02 μM in the breast cancer (MCF-7) cell line, human colorectal carcinoma (HCT116) cell line and MD Anderson-metastatic breast (MDA-MB-453) cell lines respectively. Prolonged treatment of cells with the compound resulted in apoptotic cell death as determined by cleavage of Poly (ADP-ribose) polymerase (PARP), a caspase 3 substrate and an apoptotic marker. This study, therefore, explored novel derivatives of carbothioamides for their anticancer activities; the structure activity relationship (SAR) reported in this study and predicted docking analysis and ADMET profile will help optimize carbothioamides as anticancer agents. • Synthesis of twelve different derivatives of phenyl substituted carbothioamides. • HCT116 cell line was used for the evaluation of antiproliferative activity. • Four compounds reduced colorectal cancer cell viability by more than 50 %. • Compound 11 showed strongest activity with IC 50 below 22 µM in three cell lines. • Molecular docking and ADMET were calculated

Source: Results in Chemistry

DOI: 10.1016/j.rechem.2025.102616