RESUMO
Aim: Thiophene-based heterocycles were synthesized and evaluated for their antimicrobial activity against methicillin-resistant Staphylococcus aureus, Escherichia coli, Clostridium difficile and Candida albicans strains. Methods: Antimicrobial activity was determined using the broth microdilution method. Results: Spiro-indoline-oxadiazole 17 displayed the highest activity against C. difficile while having no effects against other bacterial strains. Compounds 8 and 16 displayed strong effects against TolC, an outer membrane protein, mutant E. coli. The results of computational chemical study and outcomes of experiments were in good agreement. A molecular docking study was conducted using a molecular operating environment to simulate the binding energies of the potent compounds with D-alanine ligase protein. Conclusion: This study suggests that spiro-indoline-oxadiazole 17 could be a good anticlostridial agent.
A series of thiophene-based heterocycles was synthesized and evaluated for their antimicrobial activity against methicillin-resistant Staphylococcus aureus, Escherichia coli, Clostridium difficile and Candida albicans strains. Notablly, a spiroindolineoxadiazole derivative displayed the highest activity against C. difficile with minimum inhibitory concentration values of 2 to 4 µg/ml. Interestingly, this compound exhibited no effects against other tested bacterial strains. For C. difficile, drugs that can inhibit it without affecting other Gram-positive or Gram-negative bacteria (not affecting the normal microbiota) are needed. This compound could be a good anticlostridial agent.
