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 nu-merous biological activities in the treatment of many diseases. Thiazole-linked-thiadiazole and dithia-zole derivatives were synthesized in this context by reacting thiazole thiosemicarbazone derivatives with hydrazonoyl chlorides, phenacyl bromides, or alpha-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 Staphylo-coccus 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. (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

In the study, thiazole-linked-thiadiazole and dithiazole derivatives were synthesized and their antibacterial activity was tested. Three derivatives, 7d, 14c, and 14d, showed significant activity against Methicillin-sensitive Staphylococcus aureus (MSSA), Methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Staphylococcus aureus (VRSA). Moreover, compounds 7d, 14c, and 14d demonstrated potential anti-biofilm activity, with MSSA and MRSA being more sensitive than VRSA. Docking results also indicated that the dithiazole derivatives 14c and 14d showed good fitting and proper orientation into MRSA protein.