Exploiting Natural Maltol for Synthesis of Novel Hydroxypyridone Derivatives as Promising Anti-Virulence Agents in Bactericides Discovery

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(1H)-one derivatives and evaluated their antibacterial behaviors. Compound B6 exhibited the highest bioactivity, with half-maximal effective concentration (EC50) values ranging fro9m 10.03 to 30.16 mu g 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 B6 against rice bacterial leaf blight at 200 mu g 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 for bacterial diseases.

Automated summary

Anti-infection strategies focused on suppressing bacterial virulence factors are important for developing new antibacterial agents to combat drug resistance. In this study, we synthesized a series of 3-hydroxy-2-methyl-1-pyridin-4(1H)-one derivatives and tested their antibacterial activity. Compound B6 showed the highest bioactivity, effectively reducing various virulence factors and inhibiting the expression of virulence factor-related genes. Additionally, B6 exhibited moderate control efficiency against rice bacterial leaf blight, which was further enhanced by pesticide additives. These findings highlight the potential of targeting bacterial virulence factors as a new approach for treating bacterial diseases.