Design, Synthesis, and Anti-HIV Evaluation of Novel Triazine Derivatives Targeting the Entrance Channel of the NNRTI Binding Pocket
A novel series of triazine derivatives targeting the entrance channel of the HIV‐1 non‐nucleoside reverse transcriptase inhibitor binding pocket (NNIBP) were designed and synthesized on the basis of our previous work. The results of a cell‐based antiviral screening assay indicated that most compound...
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| Veröffentlicht in: | Chemical biology & drug design 2015-07, Vol.86 (1), p.122-128 |
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| creator | Chen, Xuwang Meng, Qing Qiu, Liyun Zhan, Peng Liu, Huiqing De Clercq, Erik Pannecouque, Christophe Liu, Xinyong |
| description | A novel series of triazine derivatives targeting the entrance channel of the HIV‐1 non‐nucleoside reverse transcriptase inhibitor binding pocket (NNIBP) were designed and synthesized on the basis of our previous work. The results of a cell‐based antiviral screening assay indicated that most compounds showed good‐to‐moderate activity against wild‐type HIV‐1 with EC50 values within the concentration range of 0.0078–0.16 μm (compound DCS‐a4, EC50 = 7.8 nm). Some compounds displayed submicromolar activity against the K103N/Y181C resistant mutant strain (such as compound DCS‐a4, EC50 = 0.65 μm). Molecular modeling studies confirmed that the new compounds could bind into the NNIBP similarly as the lead compound, and the newly introduced flexible heterocycles could occupy the entrance channel effectively. In addition, the preliminary structure–activity relationship and the RT inhibitory assay are presented in this study.
A novel series of triazine derivatives targeting the entrance channel of NNRTI were designed by combining the pharmacophoric groups of the drug etravirine and the pDAPY derivatives, which showed promising activity against HIV‐1 in MT‐4 cell line. |
| doi_str_mv | 10.1111/cbdd.12471 |
| format | Article |
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A novel series of triazine derivatives targeting the entrance channel of NNRTI were designed by combining the pharmacophoric groups of the drug etravirine and the pDAPY derivatives, which showed promising activity against HIV‐1 in MT‐4 cell line.</description><identifier>ISSN: 1747-0277</identifier><identifier>EISSN: 1747-0285</identifier><identifier>DOI: 10.1111/cbdd.12471</identifier><identifier>PMID: 25358434</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Anti-HIV Agents - chemical synthesis ; Anti-HIV Agents - chemistry ; antiviral activity ; Binding Sites ; Drug Design ; entrance channel ; HIV Reverse Transcriptase - antagonists & inhibitors ; HIV Reverse Transcriptase - chemistry ; HIV-1 ; HIV-1 - enzymology ; Molecular Docking Simulation ; molecular modeling ; NNRTIs ; Reverse Transcriptase Inhibitors - chemical synthesis ; Reverse Transcriptase Inhibitors - chemistry ; Structure-Activity Relationship ; Triazines - chemical synthesis ; Triazines - chemistry</subject><ispartof>Chemical biology & drug design, 2015-07, Vol.86 (1), p.122-128</ispartof><rights>2014 John Wiley & Sons A/S</rights><rights>2014 John Wiley & Sons A/S.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5071-6be122a723609f0dad38923bf240fa8fad9a86b8572e81e6116ac2171e01526f3</citedby><cites>FETCH-LOGICAL-c5071-6be122a723609f0dad38923bf240fa8fad9a86b8572e81e6116ac2171e01526f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fcbdd.12471$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fcbdd.12471$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25358434$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xuwang</creatorcontrib><creatorcontrib>Meng, Qing</creatorcontrib><creatorcontrib>Qiu, Liyun</creatorcontrib><creatorcontrib>Zhan, Peng</creatorcontrib><creatorcontrib>Liu, Huiqing</creatorcontrib><creatorcontrib>De Clercq, Erik</creatorcontrib><creatorcontrib>Pannecouque, Christophe</creatorcontrib><creatorcontrib>Liu, Xinyong</creatorcontrib><title>Design, Synthesis, and Anti-HIV Evaluation of Novel Triazine Derivatives Targeting the Entrance Channel of the NNRTI Binding Pocket</title><title>Chemical biology & drug design</title><addtitle>Chem Biol Drug Des</addtitle><description>A novel series of triazine derivatives targeting the entrance channel of the HIV‐1 non‐nucleoside reverse transcriptase inhibitor binding pocket (NNIBP) were designed and synthesized on the basis of our previous work. The results of a cell‐based antiviral screening assay indicated that most compounds showed good‐to‐moderate activity against wild‐type HIV‐1 with EC50 values within the concentration range of 0.0078–0.16 μm (compound DCS‐a4, EC50 = 7.8 nm). Some compounds displayed submicromolar activity against the K103N/Y181C resistant mutant strain (such as compound DCS‐a4, EC50 = 0.65 μm). Molecular modeling studies confirmed that the new compounds could bind into the NNIBP similarly as the lead compound, and the newly introduced flexible heterocycles could occupy the entrance channel effectively. In addition, the preliminary structure–activity relationship and the RT inhibitory assay are presented in this study.
A novel series of triazine derivatives targeting the entrance channel of NNRTI were designed by combining the pharmacophoric groups of the drug etravirine and the pDAPY derivatives, which showed promising activity against HIV‐1 in MT‐4 cell line.</description><subject>Anti-HIV Agents - chemical synthesis</subject><subject>Anti-HIV Agents - chemistry</subject><subject>antiviral activity</subject><subject>Binding Sites</subject><subject>Drug Design</subject><subject>entrance channel</subject><subject>HIV Reverse Transcriptase - antagonists & inhibitors</subject><subject>HIV Reverse Transcriptase - chemistry</subject><subject>HIV-1</subject><subject>HIV-1 - enzymology</subject><subject>Molecular Docking Simulation</subject><subject>molecular modeling</subject><subject>NNRTIs</subject><subject>Reverse Transcriptase Inhibitors - chemical synthesis</subject><subject>Reverse Transcriptase Inhibitors - chemistry</subject><subject>Structure-Activity Relationship</subject><subject>Triazines - chemical synthesis</subject><subject>Triazines - chemistry</subject><issn>1747-0277</issn><issn>1747-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFy0zAQhjUMDC2FCw_A6MgwddFKtiUf2zi0GTKBoaYcNbK9TkUduUhOIFx5cRTS5shedkf6_u_wE_Ia2BnEed_UbXsGPJXwhByDTGXCuMqeHm4pj8iLEL4zlqYZV8_JEc9EplKRHpM_JQa7dKf0euvG23iHU2pcS8_daJOr2Q2dbky_NqMdHB06uhg22NPKW_PbOqQleruJnxsMtDJ-iaN1Sxo9dOpGb1yDdHJrnIuZGN69LxZfqhm9sK7dkZ-H5g7Hl-RZZ_qArx72Cfn6YVpNrpL5p8vZ5HyeNBmTkOQ1AudGcpGzomOtaYUquKg7nrLOqM60hVF5rTLJUQHmALlpOEhABhnPO3FC3u699374scYw6pUNDfa9cTisg4ZcFQJA5Sqi7_Zo44cQPHb63tuV8VsNTO9K17vS9b_SI_zmwbuuV9ge0MeWIwB74KftcfsflZ5clOWjNNlnbBjx1yFj_J3OpZCZ_ra41MXH65uygrnm4i_9OZqZ</recordid><startdate>201507</startdate><enddate>201507</enddate><creator>Chen, Xuwang</creator><creator>Meng, Qing</creator><creator>Qiu, Liyun</creator><creator>Zhan, Peng</creator><creator>Liu, Huiqing</creator><creator>De Clercq, Erik</creator><creator>Pannecouque, Christophe</creator><creator>Liu, Xinyong</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><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>7X8</scope></search><sort><creationdate>201507</creationdate><title>Design, Synthesis, and Anti-HIV Evaluation of Novel Triazine Derivatives Targeting the Entrance Channel of the NNRTI Binding Pocket</title><author>Chen, Xuwang ; Meng, Qing ; Qiu, Liyun ; Zhan, Peng ; Liu, Huiqing ; De Clercq, Erik ; Pannecouque, Christophe ; Liu, Xinyong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5071-6be122a723609f0dad38923bf240fa8fad9a86b8572e81e6116ac2171e01526f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Anti-HIV Agents - chemical synthesis</topic><topic>Anti-HIV Agents - chemistry</topic><topic>antiviral activity</topic><topic>Binding Sites</topic><topic>Drug Design</topic><topic>entrance channel</topic><topic>HIV Reverse Transcriptase - antagonists & inhibitors</topic><topic>HIV Reverse Transcriptase - chemistry</topic><topic>HIV-1</topic><topic>HIV-1 - enzymology</topic><topic>Molecular Docking Simulation</topic><topic>molecular modeling</topic><topic>NNRTIs</topic><topic>Reverse Transcriptase Inhibitors - chemical synthesis</topic><topic>Reverse Transcriptase Inhibitors - chemistry</topic><topic>Structure-Activity Relationship</topic><topic>Triazines - chemical synthesis</topic><topic>Triazines - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xuwang</creatorcontrib><creatorcontrib>Meng, Qing</creatorcontrib><creatorcontrib>Qiu, Liyun</creatorcontrib><creatorcontrib>Zhan, Peng</creatorcontrib><creatorcontrib>Liu, Huiqing</creatorcontrib><creatorcontrib>De Clercq, Erik</creatorcontrib><creatorcontrib>Pannecouque, Christophe</creatorcontrib><creatorcontrib>Liu, Xinyong</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Chemical biology & drug design</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Xuwang</au><au>Meng, Qing</au><au>Qiu, Liyun</au><au>Zhan, Peng</au><au>Liu, Huiqing</au><au>De Clercq, Erik</au><au>Pannecouque, Christophe</au><au>Liu, Xinyong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design, Synthesis, and Anti-HIV Evaluation of Novel Triazine Derivatives Targeting the Entrance Channel of the NNRTI Binding Pocket</atitle><jtitle>Chemical biology & drug design</jtitle><addtitle>Chem Biol Drug Des</addtitle><date>2015-07</date><risdate>2015</risdate><volume>86</volume><issue>1</issue><spage>122</spage><epage>128</epage><pages>122-128</pages><issn>1747-0277</issn><eissn>1747-0285</eissn><abstract>A novel series of triazine derivatives targeting the entrance channel of the HIV‐1 non‐nucleoside reverse transcriptase inhibitor binding pocket (NNIBP) were designed and synthesized on the basis of our previous work. The results of a cell‐based antiviral screening assay indicated that most compounds showed good‐to‐moderate activity against wild‐type HIV‐1 with EC50 values within the concentration range of 0.0078–0.16 μm (compound DCS‐a4, EC50 = 7.8 nm). Some compounds displayed submicromolar activity against the K103N/Y181C resistant mutant strain (such as compound DCS‐a4, EC50 = 0.65 μm). Molecular modeling studies confirmed that the new compounds could bind into the NNIBP similarly as the lead compound, and the newly introduced flexible heterocycles could occupy the entrance channel effectively. In addition, the preliminary structure–activity relationship and the RT inhibitory assay are presented in this study.
A novel series of triazine derivatives targeting the entrance channel of NNRTI were designed by combining the pharmacophoric groups of the drug etravirine and the pDAPY derivatives, which showed promising activity against HIV‐1 in MT‐4 cell line.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>25358434</pmid><doi>10.1111/cbdd.12471</doi><tpages>7</tpages></addata></record> |
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| subjects | Anti-HIV Agents - chemical synthesis Anti-HIV Agents - chemistry antiviral activity Binding Sites Drug Design entrance channel HIV Reverse Transcriptase - antagonists & inhibitors HIV Reverse Transcriptase - chemistry HIV-1 HIV-1 - enzymology Molecular Docking Simulation molecular modeling NNRTIs Reverse Transcriptase Inhibitors - chemical synthesis Reverse Transcriptase Inhibitors - chemistry Structure-Activity Relationship Triazines - chemical synthesis Triazines - chemistry |
| title | Design, Synthesis, and Anti-HIV Evaluation of Novel Triazine Derivatives Targeting the Entrance Channel of the NNRTI Binding Pocket |
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