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      Histone Deacetylase Inhibitors from Marine Invertebrates

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          Abstract

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          Histone deacetylases (HDACs) are enzymes that control gene expression and are involved in the onset of serious human pathologies, including cancer; hence, their inhibitors (HDACis) have received increased attention in recent years. It is known that marine invertebrates produce significant amounts of molecules showing active pharmacological properties and an extensive spectrum of biomedical applications. This review is focused on the description of the molecular, biochemical, and, where available, physiological aspects of marine invertebrate-derived compounds that possess HDACi properties, taking into consideration their possible utilization as treatment agents against different pathological states.

          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.

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          Most cited references91

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          Global Diversity of Sponges (Porifera)

          With the completion of a single unified classification, the Systema Porifera (SP) and subsequent development of an online species database, the World Porifera Database (WPD), we are now equipped to provide a first comprehensive picture of the global biodiversity of the Porifera. An introductory overview of the four classes of the Porifera is followed by a description of the structure of our main source of data for this paper, the WPD. From this we extracted numbers of all ‘known’ sponges to date: the number of valid Recent sponges is established at 8,553, with the vast majority, 83%, belonging to the class Demospongiae. We also mapped for the first time the species richness of a comprehensive set of marine ecoregions of the world, data also extracted from the WPD. Perhaps not surprisingly, these distributions appear to show a strong bias towards collection and taxonomy efforts. Only when species richness is accumulated into large marine realms does a pattern emerge that is also recognized in many other marine animal groups: high numbers in tropical regions, lesser numbers in the colder parts of the world oceans. Preliminary similarity analysis of a matrix of species and marine ecoregions extracted from the WPD failed to yield a consistent hierarchical pattern of ecoregions into marine provinces. Global sponge diversity information is mostly generated in regional projects and resources: results obtained demonstrate that regional approaches to analytical biogeography are at present more likely to achieve insights into the biogeographic history of sponges than a global perspective, which appears currently too ambitious. We also review information on invasive sponges that might well have some influence on distribution patterns of the future.
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            Marine natural products

            A comprehensive review of 1554 new MNPs, including numerous novel and bioactive compounds from marine bacteria. This review covers the literature published between January and December in 2018 for marine natural products (MNPs), with 717 citations (706 for the period January to December 2018) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1554 in 469 papers for 2018), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included. The proportion of MNPs assigned absolute configuration over the last decade is also surveyed.
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              Lysine Acetylation Goes Global: From Epigenetics to Metabolism and Therapeutics.

              Post-translational acetylation of lysine residues has emerged as a key regulatory mechanism in all eukaryotic organisms. Originally discovered in 1963 as a unique modification of histones, acetylation marks are now found on thousands of nonhistone proteins located in virtually every cellular compartment. Here we summarize key findings in the field of protein acetylation over the past 20 years with a focus on recent discoveries in nuclear, cytoplasmic, and mitochondrial compartments. Collectively, these findings have elevated protein acetylation as a major post-translational modification, underscoring its physiological relevance in gene regulation, cell signaling, metabolism, and disease.
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                Author and article information

                Journal
                Biology (Basel)
                Biology (Basel)
                biology
                Biology
                MDPI
                2079-7737
                28 November 2020
                December 2020
                : 9
                : 12
                : 429
                Affiliations
                Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, Italy; manuela.mauro01@ 123456unipa.it (M.M.); vincenzo.arizza@ 123456unipa.it (V.A.); mirella.vazzana@ 123456unipa.it (M.V.)
                Author notes
                [* ]Correspondence: claudio.luparello@ 123456unipa.it ; Tel.: +39-91-238-97405
                Author information
                https://orcid.org/0000-0001-9821-5891
                https://orcid.org/0000-0002-8772-7143
                https://orcid.org/0000-0001-6437-9409
                Article
                biology-09-00429
                10.3390/biology9120429
                7760191
                33260710
                a35cc95a-0b36-4c7a-8374-7e5a954e7293
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 October 2020
                : 25 November 2020
                Categories
                Review

                histone deacetylase inhibitors,marine invertebrates,anticancer compounds,biomedical applications,porifera,cnidaria,echinodermata

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