Chen Zhi-Yuan, Cheng Rong-Shuang, Ayixia Wubulikasimu, Liu Yu-Shuang, Wang Kai-Bo
Jiangsu Key Laboratory of Bioactive Natural Product Research, State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University Nanjing 211198, China.
Zhongguo Zhong Yao Za Zhi. 2024 Jul;49(13):3421-3431. doi: 10.19540/j.cnki.cjcmm.20240325.601.
DNA G-quadruplex(G4) is a guanine-rich single-stranded DNA sequence that spontaneously folds into a spherical four-stranded DNA secondary structure in oncogene promoter sequences and telomeres. G4s are highly associated with the occurrence and development of cancer and have emerged as promising anticancer targets. Natural products have long been important sources of anticancer drug development. In recent years, significant progress has been made in the discovery of natural drugs targeting DNA G4s, with many DNA G4s have been confirmed as promising targets of natural products, including MYC-G4, KRAS-G4, PDGFR-β-G4, BCL-2-G4, VEGF-G4, and telomeric G4. This review summarizes the research progress in discovering natural small molecules that target DNA G4s and their binding mechanisms. It also discusses the opportunities of and challenges in developing drugs targeting DNA G4s. This review will serve as a valuable reference for the research on natural products, particularly in the development of novel antitumor medications.
DNA G-四链体(G4)是一种富含鸟嘌呤的单链DNA序列,它在癌基因启动子序列和端粒中会自发折叠成球形的四链DNA二级结构。G4与癌症的发生和发展高度相关,并已成为有前景的抗癌靶点。天然产物长期以来一直是抗癌药物开发的重要来源。近年来,在发现靶向DNA G4的天然药物方面取得了重大进展,许多DNA G4已被确认为天然产物的有前景靶点,包括MYC-G4、KRAS-G4、PDGFR-β-G4、BCL-2-G4、VEGF-G4和端粒G4。本综述总结了发现靶向DNA G4的天然小分子及其结合机制的研究进展。它还讨论了开发靶向DNA G4药物的机遇和挑战。本综述将为天然产物的研究,特别是新型抗肿瘤药物的开发提供有价值的参考。