Synthesis of 4-Hydroxy Coumarin Hybrid with 2H-Thiopyran and Imidazolidine-2,4-Dione Derivatives and the Investigation of their Antimicrobial, Anticoagulant and Cytotoxic Activities, and Molecular Docking

This study encompasses the synthesis of 2H-thiopyran-connected imidazolidine-2,4-dione (3a–h, 4, and 4a–h) derivatives and the evaluation of their anticoagulant, cytotoxic, and antimicrobial activities. A series of unique 2H-thiopyran-connected imidazolidine-2,4-dione derivatives (3a–h) was prepared using cyclisation methods; 4-hydroxycoumarin hybrid containing 2H-thiopyran-connected imidazolidine-2,4-dione derivatives (4a–h) were obtained via Knoevenagel condensation. The synthesised compounds were characterized by elemental analysis, FT-IR, NMR, and mass spectroscopy. The cytotoxic, anticoagulant, and antibacterial properties of them were assessed. The compound 4e efficiently inhibited the growth of methicillin-resistant Staphylococcus aureus compared to the positive control, whereas other compounds showed only a moderate level of activities; compound 4f demonstrated more efficient antifungal activity against the type culture, Trichophyton mentagrophytes than clotrimazole, with an MIC of 2 µg/mL. Also, the latter compound displayed higher anticoagulant activity compared to other molecules synthesized and the standard. The results of cytotoxicity activity of the compound 4f was impressive against MCF-7, HeLa, and HepG2 cancer cell lines (GI₅₀ = 0.51 ± 0.08, 0.02 ± 0.65, and 0.03 ± 0.15 µm, respectively); the compound 4f exhibited greater binding affinity than the compound 4 when employing 1KZN, 1FI4, and 1Z11 proteins in in silico molecular docking experiments. Overall, the compounds 4e, and 4f showed a wide spectrum of activities and therefore could be used as antimicrobial, anticoagulant, and cytotoxic agents.