摘要
核酸倾向于结构多态性,并且除了众所周知的DNA双螺旋以外,还可以形成许多结构。其中有一个称为G-四联体(G4)的核酸四链结构家族。这些四链体结构可以通过含有重复的鸟嘌呤富含序列的序列形成,并且非B-DNA数据库的分析表明这些序列在控制细胞增殖的基因组区域中富集,例如在c-MYC的启动子区域中, k-RAS,c-KIT,HSP90和VEGF等。用小分子靶向G4的广义概念现在普遍被认为是一种有希望的抗肿瘤治疗新方法,在癌细胞系中具有抗增殖活性的几种小分子也已被证明稳定了这些DNA结构,因此暗示G4-互动的小分子作为新的抗癌药物。在这里,我们通过靶向癌基因和主要化学支架,审查那些G4相互作用的小分子与癌症细胞系中报告的基因表达调节活性。目前获得的数据令人鼓舞,但需要进一步的努力来验证G4作为药物靶点并优化G4-相互作用小分子结构成为新的抗癌药物。
关键词: 抗癌,致癌基因,转录调控,四联体,DNA,吲哚喹啉,卟啉,药物靶点。
Current Medicinal Chemistry
Title:Oncogene Expression Modulation in Cancer Cell Lines by DNA G-Quadruplex-Interactive Small Molecules
Volume: 24 Issue: 42
关键词: 抗癌,致癌基因,转录调控,四联体,DNA,吲哚喹啉,卟啉,药物靶点。
摘要: Nucleic acids are prone to structural polymorphism and a number of structures may be formed in addition to the well-known DNA double helix. Among these is a family of nucleic acid four-stranded structures known as G-quadruplexes (G4). These quadruplex structures can be formed by sequences containing repetitive guanine-rich tracks and the analysis of Non-B-DNA database indicated an enrichment of these sequences in genomic regions controlling cellular proliferation, such as for example in the promoter regions of c- MYC, k-RAS, c-KIT, HSP90 and VEGF among others. The broad concept of G4 targeting with small molecules is now generally accepted as a promising novel approach to anticancer therapy and several small molecules with antiproliferative activity in cancer cell lines have also been shown to stabilize these DNA structures, thus suggesting a potential application of G4-interactive small molecules as new anticancer drugs. Herein we review, by targeted oncogene and main chemical scaffold, those G4-interactive small molecules with reported gene expression modulatory activity in cancer cell lines. The data obtained so far are encouraging but further efforts are needed to validate G4 as drug targets and optimize the structure of G4- interactive small molecules into new anticancer drugs.
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Cite this article as:
Oncogene Expression Modulation in Cancer Cell Lines by DNA G-Quadruplex-Interactive Small Molecules, Current Medicinal Chemistry 2017; 24 (42) . https://dx.doi.org/10.2174/0929867323666160829145055
DOI https://dx.doi.org/10.2174/0929867323666160829145055 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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