靶向G-四链体的抗肿瘤分子研究进展

Research Progress of Anti-Tumor Molecules Targeting G-Quadruplex

G-四链体(G4)是由富含鸟嘌呤的DNA或RNA序列形成的非标准核酸二级结构,多位于端粒DNA末端和致癌基因的启动子区域,与细胞衰老、癌基因表达等重要的生物学过程密切相关。由于稳定G4结构能够诱导细胞的衰老、凋亡并抑制癌基因的表达,G-四链体已经成为抗肿瘤研究的新的重要靶点。近年来,科学家设计了多种小分子G4稳定剂,研究表明相关分子通过稳定G4结构表现出良好的肿瘤抑制活性,因此以G4为靶点设计和开发新的小分子药物具有广阔的发展前景。汇总近五年来靶向不同G4结构的各类小分子配体,系统分析了其结构和抗肿瘤活性之间的关系,为新型抗肿瘤小分子药物的设计与优化奠定重要基础。

G-quadruplex(G4)is a non-canonical nucleic acid secondary structure formed by guanine-rich DNA/RNA sequences.G4 structures mostly locate at the end of telomere DNA or the promoter region of oncogenes.It is closely related to important biological processes including cell senescence and oncogene expression.Since stabilization of G4 structures can induce senescence and apoptosis of cancer cells and inhibit oncogene expression,G4 has been recognized as a new target for cancer therapy.In recent years,scientists have designed and synthesized a variety of small molecules that exhibit good antitumor activity by stabilizing G4 structures.Therefore,design and development novel small molecule drugs targeting G4 have broad prospects.In this paper,various small molecule ligands targeting different G4 structures in the past five years were summarized,and the relationship between their structures and antitumor activity was systematically analyzed,which laid an important foundation for the design and optimization of novel small molecule antitumor drugs.