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

A series of novel 4-alkoxy-3-arylfuran-2(5H)-ones as tyrosyl-tRNA synthetase inhibitors were synthesized. Of these compounds, 3-(4-hydroxyphenyl)-4-(2-morpholinoethoxy)furan-2(5H)-one (27) was the most potent. The binding model and structure–activity relationship indicate that replacement of morpholine-ring in the side chain of 27 with a substituent containing more hydrophilic groups would be more suitable for further modification. Antibacterial assay revealed that the synthetic compounds are effective against growth of Gram-positive organisms, and 27 is the most potent agent against Staphylococcus aureus ATCC 25923 with MIC50 value of 0.23 μg/mL.

A series of novel 4-alkoxy-3-arylfuran-2(5H)-ones were synthesized and evaluated for their inhibitory activity against tyrosyl-tRNA synthetase from Staphylococcus aureus. 3-(4-Hydroxyphenyl)-4-(2-morpholinoethoxy)furan-2(5H)-one (27) is the most active with IC50 = 0.10 ± 0.03 μM and is the most potent antibacterial agent against S. aureus ATCC 25923 with MIC50 value of 0.23 μg/mL.Figure optionsDownload as PowerPoint slide