2. Academic Validation
  3. Discovery of Non-antibacterial Enrofloxacin Derivatives with Emerging Antiaging Effects through Drug Repurposing and Secondary Development

Discovery of Non-antibacterial Enrofloxacin Derivatives with Emerging Antiaging Effects through Drug Repurposing and Secondary Development

  • J Med Chem. 2025 May 9. doi: 10.1021/acs.jmedchem.5c00021.
Sicong Qiao 1,  Xin Chen 2,  Youyou Chen 3,  Yihe Song 1,  Donglei Shi 3,  Zhifan Mao 1,  Jian Li 1 3 4,  Yunyuan Huang 5,  Wenwen Liu 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Material biology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
  • 2 State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • 3 Key Laboratory of Tropical Biological Resources of Ministry of Education and Hainan Engineering Research Center for Drug Screening and Evaluation, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China.
  • 4 Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832003, China.
  • 5 Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, Hubei 430079, China.
PMID: 40340340 DOI: 10.1021/acs.jmedchem.5c00021
Abstract

Aging induces dysfunction and increases the risk of chronic diseases in the elderly, positioning the development of antiaging drugs to the forefront of research. Drug repurposing offers an efficient strategy for identifying antiaging lead compounds. In this study, we employed phenotypic screening and discovered that enrofloxacin could extend the lifespan in Caenorhabditis elegans. Based on these findings, we conducted rational drug design to eliminate its Antibacterial activity while maintaining the lifespan-extending effect, with the goal of developing safe and novel antiaging compounds. Consequently, JX10 exhibited minimal Antibacterial activity and competent antiaging effects in C. elegans, senescent cells, and aged mice. In terms of its mechanism, JX10 acted as a senomorphic agent by suppressing the expression of p38 MAPK and NF-κB. Furthermore, JX10 demonstrated favorable safety and pharmacokinetic properties, supporting the feasibility of JX10 as a promising candidate with the potential for therapeutic interventions in aging and aging-related diseases.

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