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来自海洋无脊椎动物的组蛋白去乙酰化酶抑制剂

Histone Deacetylase Inhibitors from Marine Invertebrates.

作者信息

Luparello Claudio, Mauro Manuela, Arizza Vincenzo, Vazzana Mirella

机构信息

Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, Italy.

出版信息

Biology (Basel). 2020 Nov 28;9(12):429. doi: 10.3390/biology9120429.

Abstract

Histone deacetylases (HDACs) are key components of the epigenetic machinery controlling gene expression. They are involved in chromatin remodeling events via post-translational histone modifications but may also act on nonhistone proteins, influencing many fundamental cellular processes. Due to the key involvement of HDACs in serious human pathologies, including cancer, HDAC inhibitors (HDACis) have received increased attention in recent years. It is known that marine invertebrates produce significant amounts of secondary metabolites showing active pharmacological properties and an extensive spectrum of biomedical applications. The aim of this review is to gather selected studies that report the extraction and identification of marine invertebrate-derived compounds that possess HDACi properties, grouping the producing species according to their taxonomic hierarchy. The molecular, biochemical, and/or physiological aspects, where available, and modes of action of these naturally occurring HDACis will be recapitulated, taking into consideration their possible utilization for the future design of analogs with increased bioavailability and efficacy, less toxicity, and, also, higher isoform selectivity.

摘要

组蛋白去乙酰化酶(HDACs)是控制基因表达的表观遗传机制的关键组成部分。它们通过翻译后组蛋白修饰参与染色质重塑事件,但也可能作用于非组蛋白,影响许多基本的细胞过程。由于HDACs在包括癌症在内的严重人类疾病中起着关键作用,近年来HDAC抑制剂(HDACis)受到了越来越多的关注。已知海洋无脊椎动物会产生大量具有活性药理特性和广泛生物医学应用的次生代谢产物。本综述的目的是收集一些选定的研究,这些研究报告了具有HDACi特性的海洋无脊椎动物衍生化合物的提取和鉴定,并根据其分类层次对产生这些化合物的物种进行分组。在可行的情况下,将概述这些天然存在的HDACis的分子、生化和/或生理方面以及作用方式,同时考虑到它们在未来设计具有更高生物利用度和疗效、更低毒性以及更高亚型选择性的类似物方面的可能用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4976/7760191/e9074bbe4356/biology-09-00429-g001.jpg

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