Molecular Docking, Synthesis, and Preliminary Cytotoxicity Evaluation of New Anthraquinone–Thiadiazol Hybrids as Possible VEGFR-2 Inhibitors
This study synthesized a new series of anthraquinones based on anthraquinone-2-carboxylic acid and to evaluate their in vitro anticancer activity. The synthetic pathway began with the cyclization of thiosemicarbazide with carbon disulfide and anhydrous sodium carbonate, yielding 2-amino-5-mercapto-1,3,4-thiadiazole. This intermediate was subjected to S-alkylation with various benzyl chlorides to generate substituted amines, which were subsequently coupled with anthraquinone-2-carboxylic acid using thionyl chloride to afford compounds MI1–MI5. The synthesized compounds were characterized by melting-point determination, TLC, and spectroscopic techniques, including ATR-FTIR, 1H-NMR, and 13C-NMR. The docking study indicates the docking scores of MI1-MI5 are −7.318, −7.533, −6.422, −6.612, and −6.429 kcal/mol, and for sunitinib is −7.086 kcal/mol. The cytotoxic effects were evaluated against human breast (MDA-MB-231) and lung cancer (A549) cell lines using the MTT assay. Among the tested compounds, MI1 exhibited the most significant antiproliferative activity. In breast cancer cells, MI1 showed an IC50 value of 6.45 µM, which was notably lower than that of the reference drug sunitinib (17.29 µM). Similarly, MI1 demonstrated strong activity against lung cancer cells with an IC50 of 6.27 µM, compared to 7.53 µM for sunitinib. These findings suggest that MI1 is a promising candidate for further development as a potential anticancer agent.