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酰腙类化合物作为组蛋白去乙酰化酶抑制剂

Hydrazides as Inhibitors of Histone Deacetylases.

机构信息

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisbon, Portugal.

Laboratory of Medicinal Chemistry, Institute of Organic Chemistry CSIC, Juan de la Cierva, 3, 28006 Madrid, Spain.

出版信息

J Med Chem. 2024 Aug 22;67(16):13512-13533. doi: 10.1021/acs.jmedchem.4c00541. Epub 2024 Aug 2.

Abstract

In this Perspective, we have brought together available biological evidence on hydrazides as histone deacetylase inhibitors (HDACis) and as a distinct type of Zn-binding group (ZBG) to be reviewed for the first time in the literature. -Alkyl hydrazides have transformed the field, providing innovative and practical chemical tools for selective and effective inhibition of specific histone deacetylase (HDAC) enzymes, in addition to the usual hydroxamic acid and -aminoanilide ZBG-bearing HDACis. This has enabled efficient targeting of neurodegenerative diseases such as Alzheimer's disease, cancer, cardiovascular diseases, and protozoal pathologies.

摘要

在本观点中,我们汇集了可用的生物证据,将酰肼作为组蛋白去乙酰化酶抑制剂 (HDACi) ,以及作为一种独特类型的 Zn 结合基团 (ZBG) 进行综述,这在文献中尚属首次。- 烷基酰肼改变了这一领域,为选择性和有效抑制特定组蛋白去乙酰化酶 (HDAC) 酶提供了创新和实用的化学工具,除了通常的羟肟酸和 - 氨基苯甲酰胺 ZBG 结合的 HDACi 。这使得靶向治疗阿尔茨海默病、癌症、心血管疾病和原生动物病理学等神经退行性疾病变得更加高效。

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