2. Academic Validation
  3. Design and optimization of piperlongumine analogs as potent senolytics

Design and optimization of piperlongumine analogs as potent senolytics

  • Bioorg Med Chem Lett. 2023 Dec 15:98:129593. doi: 10.1016/j.bmcl.2023.129593.
Xuan Zhang 1,  Yonghan He 2,  Xingui Liu 2,  Xin Zhang 2,  Peizhong Shi 3,  Yingying Wang 3,  Daohong Zhou 4,  Guangrong Zheng 5
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry and University of Florida, Gainesville, FL, 32610, USA.
  • 2 Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA.
  • 3 Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR, 72204, USA.
  • 4 Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA; Department of Biochemistry and Structure Biology, Center of Innovative Drug Discovery, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
  • 5 Department of Medicinal Chemistry and University of Florida, Gainesville, FL, 32610, USA. Electronic address: [email protected].
PMID: 38104906 DOI: 10.1016/j.bmcl.2023.129593
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.

Keywords

Cellular senescence; Piperlongumine; Senescent cells; Senolytics; Structure activity relationship.

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