DNA G-Quadruplexes as Targets for Natural Product Drug Discovery

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外文摘要：DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked G-tetrads in G-rich DNA sequences.These structures have been found to play a crucial role in highly tran-scribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer thera-peutics.Significantly,targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins,such as MYC,BCL2,KRAS,and EGFR.Natural products have long been an important source of drug discovery,particularly in the fields of cancer and infectious diseases.Noteworthy progress has recently been made in the discovery of nat-urally occurring DNA G4-targeting drugs.Numerous DNA G4s,such as MYC-G4,BCL2-G4,KRAS-G4,PDGFR-β-G4,VEGF-G4,and telomeric-G4,have been identified as potential targets of natural products,including berberine,telomestatin,quindoline,sanguinarine,isaindigotone,and many others.Herein,we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders,focus-ing on understanding the structural recognition of DNA G4s by small molecules derived from nature.We also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.

外文关键词：

G-quadruplexNatural productsAlkaloidsCancerPromoter

作者：

Kai-Bo Wang、Yingying Wang、Jonathan Dickerhoff、Danzhou Yang

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作者单位：

Borch Department of Medicinal Chemistry and Molecular Pharmacology,College of Pharmacy,Purdue University,West Lafayette,IN 47907,USA

Jiangsu Key Laboratory of Bioactive Natural Product Research & State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009,China

Purdue Center for Cancer Research,Purdue University,West Lafayette,IN 47907,USA

Department of Chemistry,Purdue University,West Lafayette,IN 47907,USA

Purdue Institute for Drug Discovery,Purdue University,West Lafayette,IN 47907,USA

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基金：

National Institutes of HealthNational Institutes of HealthNational Institutes of HealthPurdue Center for Cancer ResearchNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaProgram for Jiangsu Province Innovative Research Scholarthe"Double First-Class"University Project

项目编号：

R01CA177585U01CA240346R01CA153821DYP30CA0231688217370782322065JSSCRC2021512CPUQNJC22_08

出版年：

2024

DOI：

10.1016/j.eng.2024.03.015

工程(英文)

CSTPCDEI

ISSN：2095-8099

年,卷(期)：2024.38(7)