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含硫杂环衍生物作为细胞毒剂在药物化学中的研究进展:十年回顾。

Expedition of sulfur-containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update.

机构信息

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.

出版信息

Med Res Rev. 2022 Jan;42(1):513-575. doi: 10.1002/med.21852. Epub 2021 Aug 28.

Abstract

This review article proposes a comprehensive report of the design strategies engaged in the development of various sulfur-bearing cytotoxic agents. The outcomes of various studies depict that the sulfur heterocyclic framework is a fundamental structure in diverse synthetic analogs representing a myriad scope of therapeutic activities. A number of five-, six- and seven-membered sulfur-containing heterocyclic scaffolds, such as thiazoles, thiadiazoles, thiazolidinediones, thiophenes, thiopyrans, benzothiazoles, benzothiophenes, thienopyrimidines, simple and modified phenothiazines, and thiazepines have been discussed. The subsequent studies of the derivatives unveiled their cytotoxic effects through multiple mechanisms (viz. inhibition of tyrosine kinases, topoisomerase I and II, tubulin, COX, DNA synthesis, and PI3K/Akt and Raf/MEK/ERK signaling pathways), and several others. Thus, our concise illustration explains the design strategy and anticancer potential of these five- and six-membered sulfur-containing heterocyclic molecules along with a brief outline on seven-membered sulfur heterocycles. The thorough assessment of antiproliferative activities with the reference drug allows a proficient assessment of the structure-activity relationships (SARs) of the diversely synthesized molecules of the series.

摘要

这篇综述文章提出了一种全面的报告,介绍了开发各种含硫细胞毒性剂所采用的设计策略。各种研究的结果表明,硫杂环骨架是代表多种治疗活性的各种合成类似物的基本结构。许多五、六和七元含硫杂环骨架,如噻唑、噻二唑、噻唑烷二酮、噻吩、硫代吡喃、苯并噻唑、苯并噻吩、噻吩嘧啶、简单和修饰的吩噻嗪以及噻嗪,都已被讨论过。随后对这些衍生物的研究揭示了它们通过多种机制(即抑制酪氨酸激酶、拓扑异构酶 I 和 II、微管蛋白、COX、DNA 合成以及 PI3K/Akt 和 Raf/MEK/ERK 信号通路)产生的细胞毒性作用,以及其他一些作用。因此,我们的简明说明解释了这些五元和六元含硫杂环分子的设计策略和抗癌潜力,并简要介绍了七元硫杂环。通过参考药物对增殖活性的全面评估,可以对该系列中各种合成分子的构效关系(SAR)进行有效的评估。

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