Synthesis,Antibacterial Activity,and Structure-Activity Relationship of Fusaric Acid Analogs

摘要

Forty-one fusaric acid analogs possessing a pyridine carboxylic acid scaffold have been synthesized.The antibacterial activity results demonstrated that compounds 5b,7b,8c,and 8d displayed strong antibacterial activities against Staphylococcus aureus ATCC25923 with minimum inhibitory concentrations(MICs)of 4-16 ug/mL.Molecular docking study indicated that these compounds have strong hydrogen-bonding interactions with TyrRS.Meanwhile,8c and 8d showed promising antibacterial activities against Pseudomonas aeruginosa ATCC9027.Compound 4 exhibited pronounced antibacterial activities against a clinically isolated multidrug-resistant strain of Escherichia coli(MIC:64 ug/mL as compared 64 ug/mL of levofloxacin and 1024 ug/mL of ceftriaxone sodium).Moreover,compound 17e displayed strong synergistic antibacterial effect with levofloxacin against the multidrug-resistant strain,decreasing the MIC value of levofloxacin to 1/16 of its original MIC.No obvious cytotoxic activities against L02 was observed for compounds 4,5b,8c,8d,17d,and 17e at 50 μM.The preliminary structure-activity relationship of fusaric acid analogs was also discussed.