Synthesis and Antimicrobial Activity of Thiophene-Based Heterocycles Derived from Thiophene-2-Carbohydrazide

Abstract

<b>Aim:</b> Thiophene-based heterocycles were synthesized and evaluated for their antimicrobial activity against methicillin-resistant <i>Staphylococcus aureus, Escherichia coli, Clostridium difficile</i> and <i>Candida albicans</i> strains. <b>Methods:</b> Antimicrobial activity was determined using the broth microdilution method. <b>Results:</b> Spiro-indoline-oxadiazole <b>17</b> displayed the highest activity against <i>C. difficile</i> while having no effects against other bacterial strains. Compounds <b>8</b> and <b>16</b> displayed strong effects against TolC, an outer membrane protein, mutant <i>E. coli</i>. 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. <b>Conclusion:</b> This study suggests that spiro-indoline-oxadiazole <b>17</b> could be a good anticlostridial agent.