Synthesis of 2-,4,-6-, and/or 7-substituted quinoline derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors and anticancer agents: 3D QSAR-assisted design
[Display omitted] Following our research for human dihydroorotate dehydrogenase (hDHODH) inhibitors as anticancer agents, herein we describe 3D QSAR-based design, synthesis and in vitro screening of 2-,4,-6-, and/or 7-substituted quinoline derivatives as hDHODH inhibitors and anticancer agents. We h...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2019-04, Vol.29 (7), p.917-922 |
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| creator | Vyas, Vivek K. Qureshi, Gulamnizami Oza, Drashti Patel, Hardik Parmar, Krupali Patel, Palak Ghate, Manjunath D. |
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Following our research for human dihydroorotate dehydrogenase (hDHODH) inhibitors as anticancer agents, herein we describe 3D QSAR-based design, synthesis and in vitro screening of 2-,4,-6-, and/or 7-substituted quinoline derivatives as hDHODH inhibitors and anticancer agents. We have designed 2-,4,-6-, and/or 7-substituted quinoline derivatives and predicted their hDHODH inhibitory activity based on 3D QSAR study on 45 substituted quinoline derivatives as hDHODH inhibitors, and also predicted toxicity. Designed compounds were docked into the binding site of hDHODH. Designed compounds which showed good predictive activity, no toxicity, and good docking score were selected for the synthesis, and in vitro screening as hDHODH inhibitors in an enzyme inhibition assay, and anticancer agents in MTT assay against cancer cell lines (HT-29 and MDA-MB-231). Synthesized compounds 7 and 14 demonstrated IC50 value of 1.56 µM and 1.22 µM, against hDHODH, respectively, and these are our lead compounds for the development of new hDHODH inhibitors and anticancer agents. |
| doi_str_mv | 10.1016/j.bmcl.2019.01.038 |
| format | Article |
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Following our research for human dihydroorotate dehydrogenase (hDHODH) inhibitors as anticancer agents, herein we describe 3D QSAR-based design, synthesis and in vitro screening of 2-,4,-6-, and/or 7-substituted quinoline derivatives as hDHODH inhibitors and anticancer agents. We have designed 2-,4,-6-, and/or 7-substituted quinoline derivatives and predicted their hDHODH inhibitory activity based on 3D QSAR study on 45 substituted quinoline derivatives as hDHODH inhibitors, and also predicted toxicity. Designed compounds were docked into the binding site of hDHODH. Designed compounds which showed good predictive activity, no toxicity, and good docking score were selected for the synthesis, and in vitro screening as hDHODH inhibitors in an enzyme inhibition assay, and anticancer agents in MTT assay against cancer cell lines (HT-29 and MDA-MB-231). Synthesized compounds 7 and 14 demonstrated IC50 value of 1.56 µM and 1.22 µM, against hDHODH, respectively, and these are our lead compounds for the development of new hDHODH inhibitors and anticancer agents.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2019.01.038</identifier><identifier>PMID: 30738663</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>3D QSAR ; Anticancer agents ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Drug Design ; hDHODH inhibitors ; Human dihydroorotate dehydrogenase (hDHODH) ; Humans ; Models, Molecular ; Molecular Structure ; Oxidoreductases Acting on CH-CH Group Donors - antagonists & inhibitors ; Quantitative Structure-Activity Relationship ; Quinolines - chemistry ; Quinolines - pharmacology ; Substituted quinolines</subject><ispartof>Bioorganic & medicinal chemistry letters, 2019-04, Vol.29 (7), p.917-922</ispartof><rights>2019 Elsevier Ltd</rights><rights>Copyright © 2019 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-53bd7ae08a579f92057c8ecb6b96f03c9a959bdf1d79451d13721abce1ab17813</citedby><cites>FETCH-LOGICAL-c356t-53bd7ae08a579f92057c8ecb6b96f03c9a959bdf1d79451d13721abce1ab17813</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2019.01.038$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30738663$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vyas, Vivek K.</creatorcontrib><creatorcontrib>Qureshi, Gulamnizami</creatorcontrib><creatorcontrib>Oza, Drashti</creatorcontrib><creatorcontrib>Patel, Hardik</creatorcontrib><creatorcontrib>Parmar, Krupali</creatorcontrib><creatorcontrib>Patel, Palak</creatorcontrib><creatorcontrib>Ghate, Manjunath D.</creatorcontrib><title>Synthesis of 2-,4,-6-, and/or 7-substituted quinoline derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors and anticancer agents: 3D QSAR-assisted design</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
Following our research for human dihydroorotate dehydrogenase (hDHODH) inhibitors as anticancer agents, herein we describe 3D QSAR-based design, synthesis and in vitro screening of 2-,4,-6-, and/or 7-substituted quinoline derivatives as hDHODH inhibitors and anticancer agents. We have designed 2-,4,-6-, and/or 7-substituted quinoline derivatives and predicted their hDHODH inhibitory activity based on 3D QSAR study on 45 substituted quinoline derivatives as hDHODH inhibitors, and also predicted toxicity. Designed compounds were docked into the binding site of hDHODH. Designed compounds which showed good predictive activity, no toxicity, and good docking score were selected for the synthesis, and in vitro screening as hDHODH inhibitors in an enzyme inhibition assay, and anticancer agents in MTT assay against cancer cell lines (HT-29 and MDA-MB-231). Synthesized compounds 7 and 14 demonstrated IC50 value of 1.56 µM and 1.22 µM, against hDHODH, respectively, and these are our lead compounds for the development of new hDHODH inhibitors and anticancer agents.</description><subject>3D QSAR</subject><subject>Anticancer agents</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Drug Design</subject><subject>hDHODH inhibitors</subject><subject>Human dihydroorotate dehydrogenase (hDHODH)</subject><subject>Humans</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>Oxidoreductases Acting on CH-CH Group Donors - antagonists & inhibitors</subject><subject>Quantitative Structure-Activity Relationship</subject><subject>Quinolines - chemistry</subject><subject>Quinolines - pharmacology</subject><subject>Substituted quinolines</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kd9uFCEUhydGY9fqC3hhuKzJMoVh_mF603Sra9Kk0WriHWHgTIfNDLTAbLKv1KeUcauXXgAh-c7vHPiy7D0lOSW0Pt_l3aTGvCCU54TmhLUvshUt6xKzklQvsxXhNcEtL3-dZG9C2BFCS1KWr7MTRhrW1jVbZU93BxsHCCYg16MCr8s1rvEaSavPnUcNDnMXoolzBI0eZ2PdaCwgDd7sZTR7CEgGNMyTtEib4aC9c95FGRfmz_UerAyAzobN9naz_YiMHUxnovNhaZJWNEpaBR7JhMbwCbEN-nZ3-R3LkMZa-uo03719m73q5Rjg3fN5mv38fP3jaotvbr98vbq8wYpVdcQV63QjgbSyanjPC1I1qgXV1R2ve8IUl7zine6pbnhZUU1ZU1DZKUgbbVrKTrOzY-6Dd48zhCgmExSMo7Tg5iAK2lZtU5U1S2hxRJV3IXjoxYM3k_QHQYlYHImdWByJxZEgVCRHqejDc_7cTaD_lfyVkoCLIwDplXsDXgRlIH2RNh5UFNqZ_-X_BrFEpBs</recordid><startdate>20190401</startdate><enddate>20190401</enddate><creator>Vyas, Vivek K.</creator><creator>Qureshi, Gulamnizami</creator><creator>Oza, Drashti</creator><creator>Patel, Hardik</creator><creator>Parmar, Krupali</creator><creator>Patel, Palak</creator><creator>Ghate, Manjunath D.</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>20190401</creationdate><title>Synthesis of 2-,4,-6-, and/or 7-substituted quinoline derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors and anticancer agents: 3D QSAR-assisted design</title><author>Vyas, Vivek K. ; Qureshi, Gulamnizami ; Oza, Drashti ; Patel, Hardik ; Parmar, Krupali ; Patel, Palak ; Ghate, Manjunath D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-53bd7ae08a579f92057c8ecb6b96f03c9a959bdf1d79451d13721abce1ab17813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>3D QSAR</topic><topic>Anticancer agents</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Drug Design</topic><topic>hDHODH inhibitors</topic><topic>Human dihydroorotate dehydrogenase (hDHODH)</topic><topic>Humans</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>Oxidoreductases Acting on CH-CH Group Donors - antagonists & inhibitors</topic><topic>Quantitative Structure-Activity Relationship</topic><topic>Quinolines - chemistry</topic><topic>Quinolines - pharmacology</topic><topic>Substituted quinolines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vyas, Vivek K.</creatorcontrib><creatorcontrib>Qureshi, Gulamnizami</creatorcontrib><creatorcontrib>Oza, Drashti</creatorcontrib><creatorcontrib>Patel, Hardik</creatorcontrib><creatorcontrib>Parmar, Krupali</creatorcontrib><creatorcontrib>Patel, Palak</creatorcontrib><creatorcontrib>Ghate, Manjunath D.</creatorcontrib><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>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vyas, Vivek K.</au><au>Qureshi, Gulamnizami</au><au>Oza, Drashti</au><au>Patel, Hardik</au><au>Parmar, Krupali</au><au>Patel, Palak</au><au>Ghate, Manjunath D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of 2-,4,-6-, and/or 7-substituted quinoline derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors and anticancer agents: 3D QSAR-assisted design</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2019-04-01</date><risdate>2019</risdate><volume>29</volume><issue>7</issue><spage>917</spage><epage>922</epage><pages>917-922</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
Following our research for human dihydroorotate dehydrogenase (hDHODH) inhibitors as anticancer agents, herein we describe 3D QSAR-based design, synthesis and in vitro screening of 2-,4,-6-, and/or 7-substituted quinoline derivatives as hDHODH inhibitors and anticancer agents. We have designed 2-,4,-6-, and/or 7-substituted quinoline derivatives and predicted their hDHODH inhibitory activity based on 3D QSAR study on 45 substituted quinoline derivatives as hDHODH inhibitors, and also predicted toxicity. Designed compounds were docked into the binding site of hDHODH. Designed compounds which showed good predictive activity, no toxicity, and good docking score were selected for the synthesis, and in vitro screening as hDHODH inhibitors in an enzyme inhibition assay, and anticancer agents in MTT assay against cancer cell lines (HT-29 and MDA-MB-231). Synthesized compounds 7 and 14 demonstrated IC50 value of 1.56 µM and 1.22 µM, against hDHODH, respectively, and these are our lead compounds for the development of new hDHODH inhibitors and anticancer agents.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30738663</pmid><doi>10.1016/j.bmcl.2019.01.038</doi><tpages>6</tpages></addata></record> |
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| subjects | 3D QSAR Anticancer agents Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Drug Design hDHODH inhibitors Human dihydroorotate dehydrogenase (hDHODH) Humans Models, Molecular Molecular Structure Oxidoreductases Acting on CH-CH Group Donors - antagonists & inhibitors Quantitative Structure-Activity Relationship Quinolines - chemistry Quinolines - pharmacology Substituted quinolines |
| title | Synthesis of 2-,4,-6-, and/or 7-substituted quinoline derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors and anticancer agents: 3D QSAR-assisted design |
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