Antibacterial Evaluation and Virtual Screening of New Thiazolyl-Triazole Schiff Bases as Potential DNA-Gyrase Inhibitors

Abstract

The global spread of bacterial resistance to drugs used in therapy requires new potent and safe antimicrobial agents. DNA gyrases represent important targets in drug discovery. Schiff bases, thiazole, and triazole derivatives are considered key scaffolds in medicinal chemistry. Fifteen thiazolyl-triazole Schiff bases were evaluated for their antibacterial activity, measuring the growth inhibition zone diameter, the minimum inhibitory concentration (MIC), and the minimum bactericidal concentration (MBC), against Gram-positive (<i>Staphylococcus aureus</i>, <i>Listeria monocytogenes</i>) and Gram-negative (<i>Escherichia coli</i>, <i>Salmonella typhimurium</i>, <i>Pseudomonas aeruginosa</i>) bacteria. The inhibition of <i>S. aureus</i> and <i>S. typhimurium</i> was modest. Compounds <b>B1</b>, <b>B2</b>, and <b>B9</b> showed a similar effect as ciprofloxacin, the antimicrobial reference, against <i>L. monocytogenes</i>. <b>B10</b> displayed a better effect. Derivatives <b>B1</b>, <b>B5</b>-<b>7</b>, <b>B9</b>, and <b>B11</b>-<b>15</b> expressed MIC values lower than the reference, against <i>L. monocytogenes</i>. <b>B5</b>, <b>B6</b>, and <b>B11</b>-<b>15</b> strongly inhibited the growth of <i>P. aeruginosa</i>. All compounds were subjected to an in silico screening of the ADMET (absorption, distribution, metabolism, elimination, toxicity) properties. Molecular docking was performed on the gyrA and gyrB from <i>L. monocytogenes</i>. The virtual screening concluded that thiazolyl-triazole Schiff base <b>B8</b> is the best <i>drug-like</i> candidate, satisfying requirements for both safety and efficacy, being more potent against the bacterial gyrA than ciprofloxacin.