3-Aryl-4-acyloxyethoxyfuran-2(5H)-ones as inhibitors of tyrosyl-tRNA synthetase: Synthesis, molecular docking and antibacterial evaluation

Thirty-eight 3-aryl-4-acyloxyethoxyfuran-2(5H)-ones were designed, prepared and tested for antibacterial activities. Some of them showed significant antibacterial activity against Gram-positive organism, Gram-negative organism and fungus. Out of these compounds, 4-(2-(3-chlorophenylformyloxy)ethoxy)-3-(4-chlorophenyl)furan-2(5H)-one (d40) showed the widest spectrum of activity with MIC50 of 2.0 mu g/mL against Staphylococcus aureus, 4.3 mu g/mL against Escherichia coli, 1.5 mu g/mL against Pseudomonas aeruginosa and 1.2 mu g/mL against Candida albicans. Our data disclosed that MIC50 values against whole cell bacteria are positive correlation with MIC50 values against tyrosyl-tRNA synthetase. Meanwhile, molecular docking of d40 into S. aureus tyrosyl-tRNA synthetase active site was also performed, and the inhibitor tightly fitting the active site might be an important reason why it has high antimicrobial activity. (C) 2013 Elsevier Ltd. All rights reserved.