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1,3,4-噁二唑类化合物作为端粒酶抑制剂:有潜力的抗癌药物。

1,3,4-Oxadiazoles as Telomerase Inhibitor: Potential Anticancer Agents.

机构信息

Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur- 495009, Chhattisgarh, India.

出版信息

Anticancer Agents Med Chem. 2018 Feb 7;17(14):1869-1883. doi: 10.2174/1871521409666170425092906.

Abstract

Cancer is a rapidly growing disease of current era which poses a major life threaten situation to human beings. Continuous research is going on in the direction to develop effective molecules for the treatment of the cancer. These efforts include searching of more active heterocyclic compounds possessing potential anticancer activity. The 1,3,4-Oxadiazole scaffold is a five member heterocyclic ring having versatile activities and created interest for synthetic organic and medicinal chemists for the designing of novel compounds having anticancer activity. The important mechanism behind tumor suppression by 1,3,4-Oxadiazole is related with the inhibition of different growth factors, enzymes and kinases etc. The current literature surveys revealed that 1,3,4-Oxadiazole is a promising lead for anti-cancer agents by the inhibition of telomerase activity. In cancerous cells telomerase enzyme is activated which maintains and restores the telomere which leads to cell proliferation. The telomerase inhibitors with enhanced specificity and improved pharmacokinetics have been considered for design and development of novel anti-cancer agents. This review focuses primarily on telomerase enzyme its function and mechanism of action. It also describes the interaction of telomerase enzyme with 1,3,4-Oxadiazole inhibitors including their structure activity relationships (SARs). With the knowledge of this molecular target, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective anti-cancer agents.

摘要

癌症是当前时代快速增长的疾病,对人类构成重大生命威胁。目前正在进行持续的研究,旨在开发治疗癌症的有效分子。这些努力包括寻找更具活性的杂环化合物,这些化合物具有潜在的抗癌活性。1,3,4-恶二唑骨架是一个五元杂环,具有多种活性,引起了合成有机和药物化学家的兴趣,他们设计具有抗癌活性的新型化合物。1,3,4-恶二唑抑制肿瘤的重要机制与不同生长因子、酶和激酶等的抑制有关。目前的文献调查表明,1,3,4-恶二唑通过抑制端粒酶活性成为有前途的抗癌药物先导物。在癌细胞中端粒酶酶被激活,维持和恢复端粒,导致细胞增殖。具有增强的特异性和改善的药代动力学的端粒酶抑制剂已被认为是设计和开发新型抗癌药物的候选物。这篇综述主要集中在端粒酶酶及其功能和作用机制上。它还描述了端粒酶酶与 1,3,4-恶二唑抑制剂的相互作用,包括它们的构效关系(SARs)。通过对这个分子靶标、结构见解和 SARs 的了解,这篇综述可能有助于(药物)化学家设计更有效、安全、选择性和具有成本效益的抗癌药物。

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