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

Abstract

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 μg/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 μg/mL as compared 64 μg/mL of levofloxacin and 1024 μg/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 LO2 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.

The Fusaric Acid Derivative qy17 Inhibits Staphylococcus haemolyticus by Disrupting Biofilm Formation and the Stress Response via Altered Gene Expression

“…Their wide availability and low cost are also advantageous for further development of this approach. In a previous report, we isolated an endophytic fungus ( Gibberella intermedia ) from Polygonum capitatum , a traditional Chinese herb that has a long history of use in treating urinary tract infections, and analyzed its metabolites ( Zhang et al, 2021 ).…”

“…However, the antibacterial effect and molecular mechanism of FA against S. haemolyticus are still unclear. Therefore, based on the previous extraction of FA from the endophytic fungus Gibberella intermedia from Polygonum capitatum , followed by its use as a template for modification and transformation, 42 derivatives were obtained, including 5-(4-butylphenyl) picolinic acid (qy17) and 5-(4-(tert-butyl) phenyl) picolinic acid (qy20) ( Zhang et al, 2021 ). Here, the antibacterial function and lineage of qy17 and qy20 were characterized.…”