Exploiting Natural Maltol for Synthesis of Novel Hydroxypyridone Derivatives as Promising Anti-Virulence Agents in Bactericides Discovery
Wan‐Lin Xiao, Na Wang, Linli Yang, Yu‐Mei Feng, Pan-Long Chu, Jiaojiao Zhang, Shuaishuai Liu, Wu‐Bin Shao, Xiang Zhou, Liwei Liu, Song Yang
Abstract
Anti-infection strategies based on suppression of bacterial virulence factors represent a crucial direction for the development of new antibacterial agents to address the resistance triggered by traditional drugs’/pesticides’ bactericidal activity. To identify and obtain more effective and diverse molecules targeting virulence, we prepared a series of 3-hydroxy-2-methyl-1-pyridin-4-(1 H )-one derivatives and evaluated their antibacterial behaviors. Compound B 6 exhibited the highest bioactivity, with half-maximal effective concentration (EC 50 ) values ranging fro9m 10.03 to 30.16 μg mL –1 against three plant pathogenic bacteria. The antibacterial mechanism showed that it could considerably reduce various virulence factors (such as extracellular enzymes, biofilm, and T3SS effectors) and inhibit the expression of virulence factor-related genes. In addition, the control efficiency of compound B 6 against rice bacterial leaf blight at 200 μg mL –1 was 46.15–49.15%, and their control efficiency was improved by approximately 12% after the addition of pesticide additives. Thus, a new class of bactericidal candidates targeting bacterial virulence factors was developed for controlling plant bacterial diseases.