ABSTRACT
The widespread and repeated use of broad-spectrum bactericides has led to an increase in resistance. Developing novel broad-spectrum bactericides cannot solve the resistance problem, and may even aggravate it. The design of specific and selective bactericides has become urgent. A specific bactericidal design strategy was proposed by introducing exogenous metabolites in this study. This strategy was used to optimize two known antibacterial agents, luteolin (M) and Isoprothiolane (D), against Xoo. Based on the prodrug principles, target compound MB and DB were synthesized by combing M or D with exogenous metabolites, respectively. Bactericidal activity test results demonstrated that while the antibacterial ability of target compounds was significantly improved, their selectivity was also well enhanced by the introducing of exogenous metabolites. Comparing with the original compound, the antibacterial activity of target compound was significantly increased 92.0% and 74.5%, respectively. The optimized target compounds were more easily absorbed, and the drug application concentrations were much lower than those of the original agents, which would greatly reduce environmental pollution and relieve resistance risk. Our proposed strategy is of great significance for exploring the specific and selective bactericides against other pathogens.
