Design and optimization of piperlongumine analogs as potent senolytics

Xuan Zhang, Yonghan He, Xingui Liu, Xin Zhang, Peizhong Shi, Yingying Wang, Daohong Zhou, Guangrong Zheng

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number129593
JournalBioorganic and Medicinal Chemistry Letters
Volume98
DOIs
StatePublished - Jan 15 2024

Keywords

  • Cellular senescence
  • Piperlongumine
  • Senescent cells
  • Senolytics
  • Structure activity relationship

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Design and optimization of piperlongumine analogs as potent senolytics'. Together they form a unique fingerprint.

Cite this