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β-内酰胺衍生物及其抗癌活性:简短综述。

β-Lactone Derivatives and Their Anticancer Activities: A Short Review.

机构信息

School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning, 437100, China.

出版信息

Curr Top Med Chem. 2021;21(18):1645-1656. doi: 10.2174/1568026621666210402142150.

Abstract

Cancers, a set of genetic diseases that can change the behavior and cell growth in body tissues, are the second leading cause of death across the world. Several treatment approaches, such as radiation, immunotherapy, and chemotherapy, can be applied to cure cancer, and among them, chemotherapy is one of the primary treatments for cancer, in which chemotherapeutic drugs are used. Great achievements have been made in the development of novel anticancer agents, but drug resistance is usually generated quickly, making overcoming drug resistance or developing more effective anticancer agents an imperative challenge. β-Lactones (2-oxetanones) are chemically diverse and often referred to as privileged structures for the discovery of new drugs, including anticancer agents. Marizomib (Salinosporamide A), a naturally occurring β-lactone proteasome inhibitor derived from the marine actinobacterium Salinispora tropica, has been termed as an orphan drug against multiple myeloma. Therefore, β-lactones are useful scaffolds for the discovery of novel anticancer agents. This review is an endeavour to highlight the advances in β-lactone derivatives with anticancer potential. The synthetic strategies, structure-activity relationships, as well as modes of action, are also discussed to pave the way for further rational design.

摘要

癌症是一组遗传疾病,可以改变体内组织的行为和细胞生长,是全球第二大致死原因。有几种治疗方法,如放疗、免疫疗法和化疗,可以用于治疗癌症,其中化疗是癌症的主要治疗方法之一,使用化疗药物。在开发新型抗癌药物方面已经取得了巨大的成就,但耐药性通常很快产生,因此克服耐药性或开发更有效的抗癌药物是一个紧迫的挑战。β-内酰胺(2-恶唑烷酮)具有化学多样性,通常被称为发现新药的特权结构,包括抗癌药物。Marizomib(Salinosporamide A)是一种天然存在的β-内酰胺蛋白酶体抑制剂,来源于海洋放线菌 Salinispora tropica,被称为治疗多发性骨髓瘤的孤儿药。因此,β-内酰胺是发现新型抗癌药物的有用支架。本综述旨在强调具有抗癌潜力的β-内酰胺衍生物的进展。还讨论了合成策略、构效关系以及作用模式,为进一步的合理设计铺平了道路。

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