Discovery of a quinoline-based senomorphic agent for the treatment of chronic kidney disease.

Youyou Chen, Sicong Qiao, Xin Chen, Linfen Li, Jiale Wu, Centao Shi, Jian Li, Yuan Guo, Yunyuan Huang, Wenwen Liu

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, Hainan Province Key Laboratory of One Health, Hainan International One Health Institute, Haikou, 570228, China. · pubmed

Paper

Abstract

Senescence is a risk factor for chronic diseases, making anti-aging interventions a promising strategy for geriatric conditions. While a non-antibacterial derivative C1 of enrofloxacin has been proposed to extend lifespan in Caenorhabditis elegans (C. elegans), its unresolved cytotoxicity in healthy mammalian cells limits its combinatory potential and safety as an anti-aging agent. With the aim of preserving anti-aging activity while enhancing safety, we here performed structural optimization of C1 and created 37 derivatives. Among them, C36, which derived from introducing an isopropoxy group at the R

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Research summary

The paper claims that a structurally optimized quinoline derivative, C36, retains senomorphic activity to treat chronic kidney disease while overcoming the cytotoxicity of the parent compound C1. This is relevant because it addresses cellular senescence, a fundamental driver of aging, by developing a safer pharmacological intervention to clear senescent cells, although the impact is limited to a specific disease application and incremental chemical optimization rather than a broad breakthrough in lifespan extension.

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