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

doi:10.1016/j.bmcl.2023.129593

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 journal › Article › peer-review

2 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 language	English (US)
Article number	129593
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	98
DOIs	https://doi.org/10.1016/j.bmcl.2023.129593
State	Published - 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

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10.1016/j.bmcl.2023.129593

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title = "Design and optimization of piperlongumine analogs as potent senolytics",

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",

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

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T1 - Design and optimization of piperlongumine analogs as potent senolytics

AU - Zhang, Xuan

AU - He, Yonghan

AU - Liu, Xingui

AU - Zhang, Xin

AU - Shi, Peizhong

AU - Wang, Yingying

AU - Zhou, Daohong

AU - Zheng, Guangrong

PY - 2024/1/15

Y1 - 2024/1/15

N2 - 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.

AB - 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.

KW - Cellular senescence

KW - Piperlongumine

KW - Senescent cells

KW - Senolytics

KW - Structure activity relationship

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Design and optimization of piperlongumine analogs as potent senolytics

Abstract

Keywords

ASJC Scopus subject areas

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