Isophthalic Acid‐Based HDAC Inhibitors as Potent Inhibitors of HDAC8 from Schistosoma mansoni
Schistosoma mansoni histone deacetylase 8 (SmHDAC8) has been recently identified as a new potential target for the treatment of schistosomiasis. A series of newly designed and synthesized alkoxyamide‐based and hydrazide‐based HDAC inhibitors were tested for inhibitory activity against SmHDAC8 and hu...
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| Veröffentlicht in: | Arch Pharm (Weinheim) 2017-08, Vol.350 (8), p.n/a |
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| creator | Stenzel, Katharina Chakrabarti, Alokta Melesina, Jelena Hansen, Finn K. Lancelot, Julien Herkenhöhner, Simon Lungerich, Beate Marek, Martin Romier, Christophe Pierce, Raymond. J. Sippl, Wolfgang Jung, Manfred Kurz, Thomas |
| description | Schistosoma mansoni histone deacetylase 8 (SmHDAC8) has been recently identified as a new potential target for the treatment of schistosomiasis. A series of newly designed and synthesized alkoxyamide‐based and hydrazide‐based HDAC inhibitors were tested for inhibitory activity against SmHDAC8 and human HDACs 1, 6, and 8. The front runner compounds showed submicromolar activity against SmHDAC8 and modest preference for SmHDAC8 over its human orthologue hHDAC8. Docking studies provided insights into the putative binding mode in SmHDAC8 and allowed rationalization of the observed selectivity profile.
A series of newly designed and synthesized alkoxyamide‐based and hydrazide‐based histone deacetylase (HDAC) inhibitors were tested for inhibitory activity against Schistosoma mansoni HDAC8 and human HDACs 1, 6, and 8. Docking studies provide insights into the putative binding mode in SmHDAC8 and allow rationalization of the observed selectivity profile. |
| doi_str_mv | 10.1002/ardp.201700096 |
| format | Article |
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A series of newly designed and synthesized alkoxyamide‐based and hydrazide‐based histone deacetylase (HDAC) inhibitors were tested for inhibitory activity against Schistosoma mansoni HDAC8 and human HDACs 1, 6, and 8. Docking studies provide insights into the putative binding mode in SmHDAC8 and allow rationalization of the observed selectivity profile.</description><identifier>ISSN: 0365-6233</identifier><identifier>EISSN: 1521-4184</identifier><identifier>DOI: 10.1002/ardp.201700096</identifier><identifier>PMID: 28639720</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Animals ; Biochemistry, Molecular Biology ; Docking studies ; HDAC8 ; Histone deacetylase inhibitors ; Histone Deacetylase Inhibitors - chemical synthesis ; Histone Deacetylase Inhibitors - chemistry ; Histone Deacetylase Inhibitors - pharmacology ; Histone Deacetylases ; Humans ; Life Sciences ; Molecular Docking Simulation ; Phthalic Acids - chemical synthesis ; Phthalic Acids - chemistry ; Phthalic Acids - pharmacology ; Repressor Proteins - antagonists & inhibitors ; Schistosoma mansoni ; Schistosoma mansoni - enzymology ; Schistosomiasis ; Schistosomicides - chemical synthesis ; Schistosomicides - chemistry ; Schistosomicides - pharmacology ; Species Specificity</subject><ispartof>Arch Pharm (Weinheim), 2017-08, Vol.350 (8), p.n/a</ispartof><rights>2017 Deutsche Pharmazeutische Gesellschaft</rights><rights>2017 Deutsche Pharmazeutische Gesellschaft.</rights><rights>2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4076-7c9e293c3b070abdc192aff244c687e5c2d5731d1e34b17fb878d1d2fad4635a3</citedby><cites>FETCH-LOGICAL-c4076-7c9e293c3b070abdc192aff244c687e5c2d5731d1e34b17fb878d1d2fad4635a3</cites><orcidid>0000-0002-9474-4224 ; 0000-0002-1648-819X ; 0000-0002-3680-935X ; 0000-0001-9820-8608 ; 0000-0002-5985-9261</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%2Fardp.201700096$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fardp.201700096$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28639720$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03691172$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Stenzel, Katharina</creatorcontrib><creatorcontrib>Chakrabarti, Alokta</creatorcontrib><creatorcontrib>Melesina, Jelena</creatorcontrib><creatorcontrib>Hansen, Finn K.</creatorcontrib><creatorcontrib>Lancelot, Julien</creatorcontrib><creatorcontrib>Herkenhöhner, Simon</creatorcontrib><creatorcontrib>Lungerich, Beate</creatorcontrib><creatorcontrib>Marek, Martin</creatorcontrib><creatorcontrib>Romier, Christophe</creatorcontrib><creatorcontrib>Pierce, Raymond. J.</creatorcontrib><creatorcontrib>Sippl, Wolfgang</creatorcontrib><creatorcontrib>Jung, Manfred</creatorcontrib><creatorcontrib>Kurz, Thomas</creatorcontrib><title>Isophthalic Acid‐Based HDAC Inhibitors as Potent Inhibitors of HDAC8 from Schistosoma mansoni</title><title>Arch Pharm (Weinheim)</title><addtitle>Arch Pharm (Weinheim)</addtitle><description>Schistosoma mansoni histone deacetylase 8 (SmHDAC8) has been recently identified as a new potential target for the treatment of schistosomiasis. A series of newly designed and synthesized alkoxyamide‐based and hydrazide‐based HDAC inhibitors were tested for inhibitory activity against SmHDAC8 and human HDACs 1, 6, and 8. The front runner compounds showed submicromolar activity against SmHDAC8 and modest preference for SmHDAC8 over its human orthologue hHDAC8. Docking studies provided insights into the putative binding mode in SmHDAC8 and allowed rationalization of the observed selectivity profile.
A series of newly designed and synthesized alkoxyamide‐based and hydrazide‐based histone deacetylase (HDAC) inhibitors were tested for inhibitory activity against Schistosoma mansoni HDAC8 and human HDACs 1, 6, and 8. Docking studies provide insights into the putative binding mode in SmHDAC8 and allow rationalization of the observed selectivity profile.</description><subject>Animals</subject><subject>Biochemistry, Molecular Biology</subject><subject>Docking studies</subject><subject>HDAC8</subject><subject>Histone deacetylase inhibitors</subject><subject>Histone Deacetylase Inhibitors - chemical synthesis</subject><subject>Histone Deacetylase Inhibitors - chemistry</subject><subject>Histone Deacetylase Inhibitors - pharmacology</subject><subject>Histone Deacetylases</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Molecular Docking Simulation</subject><subject>Phthalic Acids - chemical synthesis</subject><subject>Phthalic Acids - chemistry</subject><subject>Phthalic Acids - pharmacology</subject><subject>Repressor Proteins - antagonists & inhibitors</subject><subject>Schistosoma mansoni</subject><subject>Schistosoma mansoni - enzymology</subject><subject>Schistosomiasis</subject><subject>Schistosomicides - chemical synthesis</subject><subject>Schistosomicides - chemistry</subject><subject>Schistosomicides - pharmacology</subject><subject>Species Specificity</subject><issn>0365-6233</issn><issn>1521-4184</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0U9P2zAYBnBrYoLCuO44ReIChxS_dmI7x1DYWqkSaH_OlmM7qlESd3bKxG0fgc-4TzKXQjftspOlVz8_st8HofeAp4AxuVTBrKcEA8cYV-wNmkBJIC9AFAdogikrc0YoPULHMd4nQjEpD9EREYxWnOAJkovo16txpTqns1o78-vn05WK1mTz63qWLYaVa9zoQ8xUzO78aIfx76Fvn53I2uD77IteuTj66HuV9WqIfnDv0NtWddGevpwn6NvHm6-zeb68_bSY1ctcF5iznOvKkopq2mCOVWM0VES1LSkKzQS3pSam5BQMWFo0wNtGcGHAkFaZgtFS0RN0sctNP5Hr4HoVHqVXTs7rpdzO0i4qAE4eINnznV0H_31j4yh7F7XtOjVYv4kSKiAMGOEi0bN_6L3fhCH9JClSCFGmxSc13SkdfIzBtvsXAJbbmuS2JrmvKV348BK7aXpr9vy1lwSqHfjhOvv4nzhZf76--xP-G0GHnTo</recordid><startdate>201708</startdate><enddate>201708</enddate><creator>Stenzel, Katharina</creator><creator>Chakrabarti, Alokta</creator><creator>Melesina, Jelena</creator><creator>Hansen, Finn K.</creator><creator>Lancelot, Julien</creator><creator>Herkenhöhner, Simon</creator><creator>Lungerich, Beate</creator><creator>Marek, Martin</creator><creator>Romier, Christophe</creator><creator>Pierce, Raymond. J.</creator><creator>Sippl, Wolfgang</creator><creator>Jung, Manfred</creator><creator>Kurz, Thomas</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>K9.</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-9474-4224</orcidid><orcidid>https://orcid.org/0000-0002-1648-819X</orcidid><orcidid>https://orcid.org/0000-0002-3680-935X</orcidid><orcidid>https://orcid.org/0000-0001-9820-8608</orcidid><orcidid>https://orcid.org/0000-0002-5985-9261</orcidid></search><sort><creationdate>201708</creationdate><title>Isophthalic Acid‐Based HDAC Inhibitors as Potent Inhibitors of HDAC8 from Schistosoma mansoni</title><author>Stenzel, Katharina ; Chakrabarti, Alokta ; Melesina, Jelena ; Hansen, Finn K. ; Lancelot, Julien ; Herkenhöhner, Simon ; Lungerich, Beate ; Marek, Martin ; Romier, Christophe ; Pierce, Raymond. 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Docking studies provided insights into the putative binding mode in SmHDAC8 and allowed rationalization of the observed selectivity profile.
A series of newly designed and synthesized alkoxyamide‐based and hydrazide‐based histone deacetylase (HDAC) inhibitors were tested for inhibitory activity against Schistosoma mansoni HDAC8 and human HDACs 1, 6, and 8. Docking studies provide insights into the putative binding mode in SmHDAC8 and allow rationalization of the observed selectivity profile.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28639720</pmid><doi>10.1002/ardp.201700096</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-9474-4224</orcidid><orcidid>https://orcid.org/0000-0002-1648-819X</orcidid><orcidid>https://orcid.org/0000-0002-3680-935X</orcidid><orcidid>https://orcid.org/0000-0001-9820-8608</orcidid><orcidid>https://orcid.org/0000-0002-5985-9261</orcidid></addata></record> |
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| subjects | Animals Biochemistry, Molecular Biology Docking studies HDAC8 Histone deacetylase inhibitors Histone Deacetylase Inhibitors - chemical synthesis Histone Deacetylase Inhibitors - chemistry Histone Deacetylase Inhibitors - pharmacology Histone Deacetylases Humans Life Sciences Molecular Docking Simulation Phthalic Acids - chemical synthesis Phthalic Acids - chemistry Phthalic Acids - pharmacology Repressor Proteins - antagonists & inhibitors Schistosoma mansoni Schistosoma mansoni - enzymology Schistosomiasis Schistosomicides - chemical synthesis Schistosomicides - chemistry Schistosomicides - pharmacology Species Specificity |
| title | Isophthalic Acid‐Based HDAC Inhibitors as Potent Inhibitors of HDAC8 from Schistosoma mansoni |
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