DNA G-Quadruplexes as Targets for Natural Product Drug Discovery  

作　　者：Kai-Bo Wang Yingying Wang Jonathan Dickerhoff Danzhou Yang 

机构地区：[1]Borch Department of Medicinal Chemistry and Molecular Pharmacology,College of Pharmacy,Purdue University,West Lafayette,IN 47907,USA [2]Purdue Center for Cancer Research,Purdue University,West Lafayette,IN 47907,USA [3]Department of Chemistry,Purdue University,West Lafayette,IN 47907,USA [4]Purdue Institute for Drug Discovery,Purdue University,West Lafayette,IN 47907,USA [5]Jiangsu Key Laboratory of Bioactive Natural Product Research&State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009,China

出　　处：《Engineering》2024年第7期39-51,共13页工程（英文）

基　　金：supported by the National Institutes of Health(R01CA177585,U01CA240346,and R01CA153821)(DY);the Purdue Center for Cancer Research(P30CA023168);the National Natural Science Foundation of China(82173707 and 82322065);the Program for Jiangsu Province Innovative Research Scholar(JSSCRC2021512);the“Double First-Class”University Project(CPUQNJC22_08).

摘　　要：DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA sequences.These structures have been found to play a crucial role in highly transcribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer therapeutics.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 naturally occurring DNA G4-targeting drugs.Numerous DNA G4s,such as MYC-G4,BCL2-G4,KRAS-G4,PDGFR-b-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,focusing 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.

关 键 词：G-QUADRUPLEX Natural products ALKALOIDS CANCER PROMOTER 

分 类 号：R914[医药卫生—药物化学]