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Design and optimization of piperlongumine analogs as potent senolytics
Xuan Zhang1, Yonghan He2, Xingui Liu2
1Department of Medicinal Chemistry and University of Florida, Gainesville, FL, 32610, USA.
Abstract:
Selective removal of senescent cells (SnCs) offers a promising therapeutic strategy to treat chronic and age-related diseases. Our prior investigations led to the discovery of piperlongumine (PL) and its derivatives as senolytic agents. In this study, our medicinal chemistry campaign on both the α,β-unsaturated δ-valerolactam ring and the phenyl ring of PL culminated in the identification of compound 24, which exhibited an impressive 50-fold enhancement in senolytic activity against senescent WI-38 fibroblasts compared to PL.
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