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Drug repurposing strategy part 1: from approved drugs to agri-bactericides leads

The Journal of Antibiotics volume 76, pages 27–51 (2023)Cite this article

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Abstract

Phytopathogenic bacteria are a major cause of crop mortality and yield reduction, especially in field cultivation. The lack of effective chemistry agri-bactericides is responsible for challenging field prevention and treatment, prompting the development of long-lasting solutions to prevent, reduce, or manage some of the most devastating plant diseases facing modern agriculture today and in the future. Therefore, there is an urgent need to find lead drugs preventing and treating phytopathogenic bacterial infection. Drug repurposing, a strategy used to identify novel uses for existing approved drugs outside of their original indication, takes less time and investment than Traditional R&D Strategies in the process of drug development. Based on this method, we conduct a screen of 700 chemically diverse and potentially safe drugs against Xanthomonas oryzae PV. oryzae ACCC 11602 (Xoo), Xanthomonas axonopodis PV. citri (Xac), and Pectobacterium atrosepticum ACCC 19901 (Pa). Furthermore, the structure-activity relationship and structural similarity analysis of active drugs classify potent agri-bactericides into 8 lead series: salicylanilides, cationic nitrogen-containing drugs, azole antifungals, N-containing group, hydroxyquinolines, piperazine, kinase inhibitor and miscellaneous groups. MIC values were evaluated as antibacterial activities in this study. Identifying highly active lead compounds from the screening of approved drugs and comparison with the currently applied plant pathogenic bactericide to validate the bactericidal activity of the best candidates and assess if selected molecules or scaffolds lead to develop new antibacterial agents in the future. In conclusion, this study provides a possibility for the development of potent and highly selective agri-bactericides leads.

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Acknowledgements

This work was supported financially by the National Natural Science Foundation of China (22177043, 21877056) and The Natural Science Foundation of Gansu Province (20JR5RA311); Support was also supplied by the Key Program for international S&T cooperation projects of China Gansu Province (18YF1WA115).

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  1. These authors contributed equally: Yue Ma, Yi-Rong Wang

Authors and Affiliations

  1. School of Pharmacy, Lanzhou University, Lanzhou, 730000, People’s Republic of China

    Yue Ma, Yi-Rong Wang, Ying-Hui He, Yan-Yan Ding, Jun-Xia An, Zhi-Jun Zhang, Wen-Bin Zhao, Yong-Mei Hu & Ying-Qian Liu

  2. Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, College of Life Science, Huzhou University, Huzhou, 313000, China

    Ying-Qian Liu

  3. State Key Laboratory of Grassland Agro-ecosystems, Lanzhou University, Lanzhou, 730000, China

    Ying-Qian Liu

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Ma, Y., Wang, YR., He, YH. et al. Drug repurposing strategy part 1: from approved drugs to agri-bactericides leads. J Antibiot 76, 27–51 (2023). https://doi.org/10.1038/s41429-022-00574-y

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