David Hozain , Kevin Cottet , Yann Fromentin , Annabelle Dugay , Florence Souquet , Elisabeth Mouray , Philippe Grellier , Didier Buisson , Raimundo Gonçalves de Oliveira Junior , Marie-Christine Lallemand
{"title":"古替弗龙A的第三代类似物","authors":"David Hozain , Kevin Cottet , Yann Fromentin , Annabelle Dugay , Florence Souquet , Elisabeth Mouray , Philippe Grellier , Didier Buisson , Raimundo Gonçalves de Oliveira Junior , Marie-Christine Lallemand","doi":"10.1016/j.bmcl.2025.130186","DOIUrl":null,"url":null,"abstract":"<div><div>This study introduces third-generation derivatives of guttiferone A, designed to enhance both bioactivity and selectivity against <em>Plasmodium falciparum</em> and <em>Trypanosoma brucei</em>. Following an optimized synthetic route, two dioxolane derivatives of 3,16-oxyguttiferone A were prepared: 14-monodioxolane-3,16-oxyguttiferone A (<strong>3</strong>) and 13,14-bisdioxolane-3,16-oxyguttiferone A (<strong>4</strong>). Biological evaluation revealed compound <strong>3</strong> to be the most effective, with a selectivity index (SI) of 457.1 against <em>Trypanosoma brucei brucei</em> strain and 57.1 against <em>P. falciparum</em>, significantly outperforming its precursors. Compound <strong>4</strong> also demonstrated substantial activity with an SI of 143.8 against <em>T. brucei</em>. These results highlight the potential of targeted structural modifications, particularly monodioxolane substitution, to improve the pharmacological profile of guttiferone A derivatives.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"122 ","pages":"Article 130186"},"PeriodicalIF":2.2000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Third-generation analogues of Guttiferone A\",\"authors\":\"David Hozain , Kevin Cottet , Yann Fromentin , Annabelle Dugay , Florence Souquet , Elisabeth Mouray , Philippe Grellier , Didier Buisson , Raimundo Gonçalves de Oliveira Junior , Marie-Christine Lallemand\",\"doi\":\"10.1016/j.bmcl.2025.130186\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>This study introduces third-generation derivatives of guttiferone A, designed to enhance both bioactivity and selectivity against <em>Plasmodium falciparum</em> and <em>Trypanosoma brucei</em>. Following an optimized synthetic route, two dioxolane derivatives of 3,16-oxyguttiferone A were prepared: 14-monodioxolane-3,16-oxyguttiferone A (<strong>3</strong>) and 13,14-bisdioxolane-3,16-oxyguttiferone A (<strong>4</strong>). Biological evaluation revealed compound <strong>3</strong> to be the most effective, with a selectivity index (SI) of 457.1 against <em>Trypanosoma brucei brucei</em> strain and 57.1 against <em>P. falciparum</em>, significantly outperforming its precursors. Compound <strong>4</strong> also demonstrated substantial activity with an SI of 143.8 against <em>T. brucei</em>. These results highlight the potential of targeted structural modifications, particularly monodioxolane substitution, to improve the pharmacological profile of guttiferone A derivatives.</div></div>\",\"PeriodicalId\":256,\"journal\":{\"name\":\"Bioorganic & Medicinal Chemistry Letters\",\"volume\":\"122 \",\"pages\":\"Article 130186\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioorganic & Medicinal Chemistry Letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0960894X25000952\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/3/12 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry Letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0960894X25000952","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/12 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
This study introduces third-generation derivatives of guttiferone A, designed to enhance both bioactivity and selectivity against Plasmodium falciparum and Trypanosoma brucei. Following an optimized synthetic route, two dioxolane derivatives of 3,16-oxyguttiferone A were prepared: 14-monodioxolane-3,16-oxyguttiferone A (3) and 13,14-bisdioxolane-3,16-oxyguttiferone A (4). Biological evaluation revealed compound 3 to be the most effective, with a selectivity index (SI) of 457.1 against Trypanosoma brucei brucei strain and 57.1 against P. falciparum, significantly outperforming its precursors. Compound 4 also demonstrated substantial activity with an SI of 143.8 against T. brucei. These results highlight the potential of targeted structural modifications, particularly monodioxolane substitution, to improve the pharmacological profile of guttiferone A derivatives.
期刊介绍：
Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.
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