Synthesis of novel series of heterocyclic compounds having two azoles against Methicillin-sensitive Staphylococcus aureus

In the pharmaceutical industry, both thiazole-linked-thiadiazoles and dithiazoles are known for their numerous biological activities in the treatment of many diseases. Thiazole-linked-thiadiazole and dithiazole derivatives were synthesized in this context by reacting thiazole thiosemicarbazone derivatives with hydrazonoyl chlorides, phenacyl bromides, or α‑chloro-acetyl acetone. All proposed product structures were validated using spectral (IR, NMR, and Mass) data. The antibacterial activity of all synthesized thiazole-linked-thiadiazoles and dithiazole derivatives was tested against Methicillin-sensitive Staphylococcus aureus (MSSA) ATCC 29,213, Methicillin-resistant Staphylococcus aureus (MRSA) ATCC 700,788, and vancomycin-resistant Staphylococcus aureus (VRSA) RCMB 28,354. Three derivatives, 7d, 14c, and 14d, demonstrated significant activity. Furthermore, compounds 7d, 14c, and 14d demonstrated potential anti-biofilm activity against the three tested bacterial strains (14d > 7d > 14c), with MSSA and MRSA being more sensitive than VRSA. Further to that, docking results indicated that the dithiazole derivatives 14c and 14d were well-fitting and properly oriented into MRSA protein (PDB ID 1MWT), with docking scores of -6.077 and -6.0886 Kcal/mol.