Largazole Analogues as Histone Deacetylase Inhibitors and Anticancer Agents: An Overview of Structure–Activity Relationships
Since the time of its identification, the natural compound largazole rapidly caught the attention of the medicinal chemistry community for its impressive potency as an inhibitor of histone deacetylases (HDACs) and its strong antiproliferative activity against a broad panel of cancer cell lines. The...
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| Veröffentlicht in: | ChemMedChem 2017-12, Vol.12 (23), p.1917-1926 |
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| creator | Poli, Giulio Di Fabio, Romano Ferrante, Luca Summa, Vincenzo Botta, Maurizio |
| description | Since the time of its identification, the natural compound largazole rapidly caught the attention of the medicinal chemistry community for its impressive potency as an inhibitor of histone deacetylases (HDACs) and its strong antiproliferative activity against a broad panel of cancer cell lines. The design of largazole analogues is an expanding field of study, due to their remarkable potential as novel anticancer therapeutics. At present, a large ensemble of largazole analogues has been reported, allowing the identification of important structure–activity relationships (SAR) that can guide the design of novel compounds with improved HDAC inhibitory profiles, anticancer activity, and pharmacokinetic properties. The aim of this review is to concisely summarize the information obtained by biological evaluations of the various largazole analogues reported to date, with particular attention given to the latest analogues, as well as to analyze the various SAR obtained from this data, with the purpose of providing useful guidelines for the development of novel potent and selective HDAC inhibitors to be used as anticancer agents.
The power of depsipeptides: This review summarizes the various analogues obtained by structural modification of largazole, a natural depsipeptide characterized by impressive activity as a histone deacetylase inhibitor and anticancer agent. The main structure–activity relationships derived by biological evaluation of these compounds are analyzed and discussed, providing useful guidelines for the design of new anticancer agents. |
| doi_str_mv | 10.1002/cmdc.201700563 |
| format | Article |
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The power of depsipeptides: This review summarizes the various analogues obtained by structural modification of largazole, a natural depsipeptide characterized by impressive activity as a histone deacetylase inhibitor and anticancer agent. The main structure–activity relationships derived by biological evaluation of these compounds are analyzed and discussed, providing useful guidelines for the design of new anticancer agents.</description><identifier>ISSN: 1860-7179</identifier><identifier>EISSN: 1860-7187</identifier><identifier>DOI: 10.1002/cmdc.201700563</identifier><identifier>PMID: 29117473</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Animals ; Anticancer properties ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Antitumor activity ; Antitumor agents ; Cancer ; Depsipeptides - chemical synthesis ; Depsipeptides - chemistry ; Depsipeptides - pharmacology ; Dose-Response Relationship, Drug ; Histone deacetylase ; Histone Deacetylase Inhibitors - chemical synthesis ; Histone Deacetylase Inhibitors - chemistry ; Histone Deacetylase Inhibitors - pharmacology ; Histone Deacetylases - metabolism ; Humans ; hydrolases ; Inhibitors ; macrocyclic ligands ; Molecular Conformation ; natural products ; Pharmacology ; Structure-Activity Relationship ; Structure-activity relationships ; Thiazoles - chemical synthesis ; Thiazoles - chemistry ; Thiazoles - pharmacology ; Tumor cell lines</subject><ispartof>ChemMedChem, 2017-12, Vol.12 (23), p.1917-1926</ispartof><rights>2017 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><rights>2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3733-8422b72499015da4b4d5b1c74c4b3c2b870d300425fc3d1f5a2cd4dd8d5d7363</citedby><cites>FETCH-LOGICAL-c3733-8422b72499015da4b4d5b1c74c4b3c2b870d300425fc3d1f5a2cd4dd8d5d7363</cites><orcidid>0000-0002-8061-5632</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcmdc.201700563$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcmdc.201700563$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29117473$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Poli, Giulio</creatorcontrib><creatorcontrib>Di Fabio, Romano</creatorcontrib><creatorcontrib>Ferrante, Luca</creatorcontrib><creatorcontrib>Summa, Vincenzo</creatorcontrib><creatorcontrib>Botta, Maurizio</creatorcontrib><title>Largazole Analogues as Histone Deacetylase Inhibitors and Anticancer Agents: An Overview of Structure–Activity Relationships</title><title>ChemMedChem</title><addtitle>ChemMedChem</addtitle><description>Since the time of its identification, the natural compound largazole rapidly caught the attention of the medicinal chemistry community for its impressive potency as an inhibitor of histone deacetylases (HDACs) and its strong antiproliferative activity against a broad panel of cancer cell lines. The design of largazole analogues is an expanding field of study, due to their remarkable potential as novel anticancer therapeutics. At present, a large ensemble of largazole analogues has been reported, allowing the identification of important structure–activity relationships (SAR) that can guide the design of novel compounds with improved HDAC inhibitory profiles, anticancer activity, and pharmacokinetic properties. The aim of this review is to concisely summarize the information obtained by biological evaluations of the various largazole analogues reported to date, with particular attention given to the latest analogues, as well as to analyze the various SAR obtained from this data, with the purpose of providing useful guidelines for the development of novel potent and selective HDAC inhibitors to be used as anticancer agents.
The power of depsipeptides: This review summarizes the various analogues obtained by structural modification of largazole, a natural depsipeptide characterized by impressive activity as a histone deacetylase inhibitor and anticancer agent. The main structure–activity relationships derived by biological evaluation of these compounds are analyzed and discussed, providing useful guidelines for the design of new anticancer agents.</description><subject>Animals</subject><subject>Anticancer properties</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antitumor activity</subject><subject>Antitumor agents</subject><subject>Cancer</subject><subject>Depsipeptides - chemical synthesis</subject><subject>Depsipeptides - chemistry</subject><subject>Depsipeptides - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Histone deacetylase</subject><subject>Histone Deacetylase Inhibitors - chemical synthesis</subject><subject>Histone Deacetylase Inhibitors - chemistry</subject><subject>Histone Deacetylase Inhibitors - pharmacology</subject><subject>Histone Deacetylases - metabolism</subject><subject>Humans</subject><subject>hydrolases</subject><subject>Inhibitors</subject><subject>macrocyclic ligands</subject><subject>Molecular Conformation</subject><subject>natural products</subject><subject>Pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>Structure-activity relationships</subject><subject>Thiazoles - chemical synthesis</subject><subject>Thiazoles - chemistry</subject><subject>Thiazoles - pharmacology</subject><subject>Tumor cell lines</subject><issn>1860-7179</issn><issn>1860-7187</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0ctOGzEUBmALgQql3bKsLLHpJsG3GXvYRaFcpFRIlP3IY58JRpNxsD1B6aLiHfqGPEkdhaZSN6xsWZ9_6ZwfoRNKxpQQdmYW1owZoZKQouR76IiqkowkVXJ_d5fVIfoY4yMhQiiqPqBDVlEqheRH6NdMh7n-6TvAk153fj5AxDriaxeT7wFfgDaQ1p2OgG_6B9e45EMWvc0-OaN7AwFP5tCneJ6f8O0KwsrBM_Yt_pHCYNIQ4PXl98Qkt3Jpje-g08n5Pj64ZfyEDlrdRfj8dh6j-8tv99Pr0ez26mY6mY0Ml5yPlGCskUxUFaGF1aIRtmiokcKIhhvWKEksz-OxojXc0rbQzFhhrbKFlbzkx-jrNnYZ_FOeMNULFw10ne7BD7GmVckEpwVVmZ7-Rx_9EPJqNkpyVpWF2qjxVpngYwzQ1svgFjqsa0rqTTH1pph6V0z-8OUtdmgWYHf8bxMZVFvw7DpYvxNXT79fTP-F_wGrIZv2</recordid><startdate>20171207</startdate><enddate>20171207</enddate><creator>Poli, Giulio</creator><creator>Di Fabio, Romano</creator><creator>Ferrante, Luca</creator><creator>Summa, Vincenzo</creator><creator>Botta, Maurizio</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8061-5632</orcidid></search><sort><creationdate>20171207</creationdate><title>Largazole Analogues as Histone Deacetylase Inhibitors and Anticancer Agents: An Overview of Structure–Activity Relationships</title><author>Poli, Giulio ; Di Fabio, Romano ; Ferrante, Luca ; Summa, Vincenzo ; Botta, Maurizio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3733-8422b72499015da4b4d5b1c74c4b3c2b870d300425fc3d1f5a2cd4dd8d5d7363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Anticancer properties</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antitumor activity</topic><topic>Antitumor agents</topic><topic>Cancer</topic><topic>Depsipeptides - chemical synthesis</topic><topic>Depsipeptides - chemistry</topic><topic>Depsipeptides - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Histone deacetylase</topic><topic>Histone Deacetylase Inhibitors - chemical synthesis</topic><topic>Histone Deacetylase Inhibitors - chemistry</topic><topic>Histone Deacetylase Inhibitors - pharmacology</topic><topic>Histone Deacetylases - metabolism</topic><topic>Humans</topic><topic>hydrolases</topic><topic>Inhibitors</topic><topic>macrocyclic ligands</topic><topic>Molecular Conformation</topic><topic>natural products</topic><topic>Pharmacology</topic><topic>Structure-Activity Relationship</topic><topic>Structure-activity relationships</topic><topic>Thiazoles - chemical synthesis</topic><topic>Thiazoles - chemistry</topic><topic>Thiazoles - pharmacology</topic><topic>Tumor cell lines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Poli, Giulio</creatorcontrib><creatorcontrib>Di Fabio, Romano</creatorcontrib><creatorcontrib>Ferrante, Luca</creatorcontrib><creatorcontrib>Summa, Vincenzo</creatorcontrib><creatorcontrib>Botta, Maurizio</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>ChemMedChem</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Poli, Giulio</au><au>Di Fabio, Romano</au><au>Ferrante, Luca</au><au>Summa, Vincenzo</au><au>Botta, Maurizio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Largazole Analogues as Histone Deacetylase Inhibitors and Anticancer Agents: An Overview of Structure–Activity Relationships</atitle><jtitle>ChemMedChem</jtitle><addtitle>ChemMedChem</addtitle><date>2017-12-07</date><risdate>2017</risdate><volume>12</volume><issue>23</issue><spage>1917</spage><epage>1926</epage><pages>1917-1926</pages><issn>1860-7179</issn><eissn>1860-7187</eissn><abstract>Since the time of its identification, the natural compound largazole rapidly caught the attention of the medicinal chemistry community for its impressive potency as an inhibitor of histone deacetylases (HDACs) and its strong antiproliferative activity against a broad panel of cancer cell lines. The design of largazole analogues is an expanding field of study, due to their remarkable potential as novel anticancer therapeutics. At present, a large ensemble of largazole analogues has been reported, allowing the identification of important structure–activity relationships (SAR) that can guide the design of novel compounds with improved HDAC inhibitory profiles, anticancer activity, and pharmacokinetic properties. The aim of this review is to concisely summarize the information obtained by biological evaluations of the various largazole analogues reported to date, with particular attention given to the latest analogues, as well as to analyze the various SAR obtained from this data, with the purpose of providing useful guidelines for the development of novel potent and selective HDAC inhibitors to be used as anticancer agents.
The power of depsipeptides: This review summarizes the various analogues obtained by structural modification of largazole, a natural depsipeptide characterized by impressive activity as a histone deacetylase inhibitor and anticancer agent. The main structure–activity relationships derived by biological evaluation of these compounds are analyzed and discussed, providing useful guidelines for the design of new anticancer agents.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29117473</pmid><doi>10.1002/cmdc.201700563</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-8061-5632</orcidid></addata></record> |
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| subjects | Animals Anticancer properties Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Antitumor activity Antitumor agents Cancer Depsipeptides - chemical synthesis Depsipeptides - chemistry Depsipeptides - pharmacology Dose-Response Relationship, Drug Histone deacetylase Histone Deacetylase Inhibitors - chemical synthesis Histone Deacetylase Inhibitors - chemistry Histone Deacetylase Inhibitors - pharmacology Histone Deacetylases - metabolism Humans hydrolases Inhibitors macrocyclic ligands Molecular Conformation natural products Pharmacology Structure-Activity Relationship Structure-activity relationships Thiazoles - chemical synthesis Thiazoles - chemistry Thiazoles - pharmacology Tumor cell lines |
| title | Largazole Analogues as Histone Deacetylase Inhibitors and Anticancer Agents: An Overview of Structure–Activity Relationships |
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