Discovery of novel ursolic acid derivatives as effective antimicrobial agents through a ROS-mediated apoptosis mechanism

Abstract

In response to the reduction of food production and economic losses caused by plant bacterial diseases, it is necessary to develop new, efficient, and green pesticides. Natural products are rich and sustainable source for the development of new pesticides due to their low toxicity, easy degradation, and eco-friendliness. In this study, we prepared three series of ursolic acid derivatives and assessed their antibacterial ability. Most target compounds exhibited outstanding antibacterial activities. Among them, the relative optimal EC₅₀ values of Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri were 2.23 (A17) and 1.39 (A16) μg·mL^–1, respectively. The antimicrobial mechanism showed that compound A17 induced an excessive accumulation and production of reactive oxygen species in bacteria and damaged the cell membrane integrity to kill bacteria. More interestingly, the addition of low concentrations of exogenous hydrogen peroxide enhanced the antibacterial efficacy of compound A17 against Xanthomonas oryzae pv. oryzae. These entertaining results suggested that compound A17 induced an apparent apoptotic behavior in the tested bacteria. Overall, we developed the promising antimicrobial agents that destroyed the redox system of phytopathogenic bacteria, further demonstrating the unprecedented potential of ursolic acid for agricultural applications.

Graphical abstract

Keywords

ursolic acid / antibacterial activities / reactive oxygen species / apoptosis

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Competing interests

The authors declare that they have no competing interests.

Acknowledgements

We acknowledge the supports from National Key Research and Development Program of China (Grant No. 2022YFD1700300), National Natural Science Foundation of China (Grant Nos. 21877021, 32160661, 32202359), the Guizhou Provincial S&T Project (Grant No. 2018[4007]), the Guizhou Province (Qianjiaohe KY number (2020)004), and Program of Introducing Talents of Discipline to Universities of China (D20023, 111 Program).

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11705-023-2361-5 and is accessible for authorized users.

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