Antimalarial activity of 2,6-dibenzylidenecyclohexanone derivatives
[Display omitted] Malaria remains one of the deadliest infectious diseases worldwide and continues to infect hundreds of millions of individuals each year. Here we report the discovery and derivatization of a series of 2,6-dibenzylidenecyclohexanones targeting the chloroquine-sensitive 3D7 strain of...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2021-09, Vol.47, p.128216-128216, Article 128216 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 47 |
| creator | Eagon, Scott Hammill, Jared T. Fitzsimmons, Kasey Sienko, Natalie Nguyen, Brandon Law, Jarvis Manjunath, Aashrita Wilkinson, Steven P. Thompson, Kara Glidden, Julia Elizabeth Rice, Amy L. Falade, Mofolusho O. Kimball, Joshua J. DiBernardo, Celine Guy, R. Kiplin |
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Malaria remains one of the deadliest infectious diseases worldwide and continues to infect hundreds of millions of individuals each year. Here we report the discovery and derivatization of a series of 2,6-dibenzylidenecyclohexanones targeting the chloroquine-sensitive 3D7 strain of Plasmodium falciparum . While the initial lead compound displayed significant toxicity in a human cell proliferation assay, we were able to identify a derivative with no detectable toxicity and sub-micromolar potency. |
| doi_str_mv | 10.1016/j.bmcl.2021.128216 |
| format | Article |
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Malaria remains one of the deadliest infectious diseases worldwide and continues to infect hundreds of millions of individuals each year. Here we report the discovery and derivatization of a series of 2,6-dibenzylidenecyclohexanones targeting the chloroquine-sensitive 3D7 strain of Plasmodium falciparum . While the initial lead compound displayed significant toxicity in a human cell proliferation assay, we were able to identify a derivative with no detectable toxicity and sub-micromolar potency.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2021.128216</identifier><identifier>PMID: 34157390</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>2,6-Dibenzylidenecyclohexanone ; Antimalarials - chemical synthesis ; Antimalarials - chemistry ; Antimalarials - pharmacology ; Cell Proliferation - drug effects ; Chloroquine - chemical synthesis ; Chloroquine - chemistry ; Chloroquine - pharmacology ; Dose-Response Relationship, Drug ; Fibroblasts - drug effects ; Humans ; Malaria ; Michael system ; Molecular Structure ; Parasitic Sensitivity Tests ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Structure activity relationship</subject><ispartof>Bioorganic & medicinal chemistry letters, 2021-09, Vol.47, p.128216-128216, Article 128216</ispartof><rights>2021 The Author(s)</rights><rights>Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-2850714cf50596a0172ac22aee542939279cdf845fddfc7a95c81a098939ef383</citedby><cites>FETCH-LOGICAL-c400t-2850714cf50596a0172ac22aee542939279cdf845fddfc7a95c81a098939ef383</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.2021.128216$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34157390$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eagon, Scott</creatorcontrib><creatorcontrib>Hammill, Jared T.</creatorcontrib><creatorcontrib>Fitzsimmons, Kasey</creatorcontrib><creatorcontrib>Sienko, Natalie</creatorcontrib><creatorcontrib>Nguyen, Brandon</creatorcontrib><creatorcontrib>Law, Jarvis</creatorcontrib><creatorcontrib>Manjunath, Aashrita</creatorcontrib><creatorcontrib>Wilkinson, Steven P.</creatorcontrib><creatorcontrib>Thompson, Kara</creatorcontrib><creatorcontrib>Glidden, Julia Elizabeth</creatorcontrib><creatorcontrib>Rice, Amy L.</creatorcontrib><creatorcontrib>Falade, Mofolusho O.</creatorcontrib><creatorcontrib>Kimball, Joshua J.</creatorcontrib><creatorcontrib>DiBernardo, Celine</creatorcontrib><creatorcontrib>Guy, R. Kiplin</creatorcontrib><title>Antimalarial activity of 2,6-dibenzylidenecyclohexanone derivatives</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
Malaria remains one of the deadliest infectious diseases worldwide and continues to infect hundreds of millions of individuals each year. Here we report the discovery and derivatization of a series of 2,6-dibenzylidenecyclohexanones targeting the chloroquine-sensitive 3D7 strain of Plasmodium falciparum . While the initial lead compound displayed significant toxicity in a human cell proliferation assay, we were able to identify a derivative with no detectable toxicity and sub-micromolar potency.</description><subject>2,6-Dibenzylidenecyclohexanone</subject><subject>Antimalarials - chemical synthesis</subject><subject>Antimalarials - chemistry</subject><subject>Antimalarials - pharmacology</subject><subject>Cell Proliferation - drug effects</subject><subject>Chloroquine - chemical synthesis</subject><subject>Chloroquine - chemistry</subject><subject>Chloroquine - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Fibroblasts - drug effects</subject><subject>Humans</subject><subject>Malaria</subject><subject>Michael system</subject><subject>Molecular Structure</subject><subject>Parasitic Sensitivity Tests</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Structure activity relationship</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLAzEUhYMotlb_gAvp0oVTbzLJTAJuSvEFBTcK7kKa3MGUedRkWhx_vVOmunR1F_c7B85HyCWFGQWa3a5nq8qWMwaMziiTjGZHZEx5xpOUgzgmY1AZJFLx9xE5i3ENQDlwfkpGKaciTxWMyWJet74ypQnelFNjW7_zbTdtiim7yRLnV1h_d6V3WKPtbNl84JepmxqnDoPfmR7HeE5OClNGvDjcCXl7uH9dPCXLl8fnxXyZWA7QJkwKyCm3hQChMgM0Z8YyZhAFZypVLFfWFZKLwrnC5kYJK6kBJfsfFqlMJ-R66N2E5nOLsdWVjxbL0tTYbKNmgnMupFSiR9mA2tDEGLDQm9DPDJ2moPfy9Frv5em9PD3I60NXh_7tqkL3F_m11QN3A4D9yp3HoKP1WFt0PqBttWv8f_0_GUt_sw</recordid><startdate>20210901</startdate><enddate>20210901</enddate><creator>Eagon, Scott</creator><creator>Hammill, Jared T.</creator><creator>Fitzsimmons, Kasey</creator><creator>Sienko, Natalie</creator><creator>Nguyen, Brandon</creator><creator>Law, Jarvis</creator><creator>Manjunath, Aashrita</creator><creator>Wilkinson, Steven P.</creator><creator>Thompson, Kara</creator><creator>Glidden, Julia Elizabeth</creator><creator>Rice, Amy L.</creator><creator>Falade, Mofolusho O.</creator><creator>Kimball, Joshua J.</creator><creator>DiBernardo, Celine</creator><creator>Guy, R. 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Kiplin</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eagon, Scott</au><au>Hammill, Jared T.</au><au>Fitzsimmons, Kasey</au><au>Sienko, Natalie</au><au>Nguyen, Brandon</au><au>Law, Jarvis</au><au>Manjunath, Aashrita</au><au>Wilkinson, Steven P.</au><au>Thompson, Kara</au><au>Glidden, Julia Elizabeth</au><au>Rice, Amy L.</au><au>Falade, Mofolusho O.</au><au>Kimball, Joshua J.</au><au>DiBernardo, Celine</au><au>Guy, R. Kiplin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antimalarial activity of 2,6-dibenzylidenecyclohexanone derivatives</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2021-09-01</date><risdate>2021</risdate><volume>47</volume><spage>128216</spage><epage>128216</epage><pages>128216-128216</pages><artnum>128216</artnum><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
Malaria remains one of the deadliest infectious diseases worldwide and continues to infect hundreds of millions of individuals each year. Here we report the discovery and derivatization of a series of 2,6-dibenzylidenecyclohexanones targeting the chloroquine-sensitive 3D7 strain of Plasmodium falciparum . While the initial lead compound displayed significant toxicity in a human cell proliferation assay, we were able to identify a derivative with no detectable toxicity and sub-micromolar potency.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>34157390</pmid><doi>10.1016/j.bmcl.2021.128216</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 2,6-Dibenzylidenecyclohexanone Antimalarials - chemical synthesis Antimalarials - chemistry Antimalarials - pharmacology Cell Proliferation - drug effects Chloroquine - chemical synthesis Chloroquine - chemistry Chloroquine - pharmacology Dose-Response Relationship, Drug Fibroblasts - drug effects Humans Malaria Michael system Molecular Structure Parasitic Sensitivity Tests Plasmodium falciparum Plasmodium falciparum - drug effects Structure activity relationship |
| title | Antimalarial activity of 2,6-dibenzylidenecyclohexanone derivatives |
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