Articles producció científica> Química Analítica i Química Orgànica

Bridgehead Modifications of Englerin A Reduce TRPC4 Activity and Intravenous Toxicity but not Cell Growth Inhibition

  • Datos identificativos

    Identificador: imarina:9296648
    Autores:
    Wu, ZhenhuaSuppo, Jean-SimonTumova, SarkaStrope, JonathanBravo, FernandoMoy, MelodyWeinstein, Ethan S.Peer, Cody J.Figg, William D.Chain, William J.Echavarren, Antonio M.Beech, David J.Beutler, John A.
    Resumen:
    Modifications at the bridgehead position of englerin A were made to explore the effects of variation at this site on the molecule for biological activity, as judged by the NCI 60 screen, in which englerin A is highly potent and selective for renal cancer cells. Replacement of the isopropyl group by other, larger substituents yielded compounds which displayed excellent selectivity and potency comparable to the natural product. Selected compounds were also evaluated for their effect on the ion channel TRPC4 as well as for intravenous toxicity in mice, and these had lower potency in both assays compared to englerin A.
  • Otros:

    Autor según el artículo: Wu, Zhenhua; Suppo, Jean-Simon; Tumova, Sarka; Strope, Jonathan; Bravo, Fernando; Moy, Melody; Weinstein, Ethan S.; Peer, Cody J.; Figg, William D.; Chain, William J.; Echavarren, Antonio M.; Beech, David J.; Beutler, John A.;
    Departamento: Química Analítica i Química Orgànica
    Autor/es de la URV: BRAVO LARA, FERNANDO / ECHAVARREN PABLOS, ANTONIO
    Palabras clave: Trpc4 Tonantzitlolone Pkc-theta Mice Kidney cancer Ion channels Formal synthesis Englerin Cytotoxicity Channels Biological evaluation (-)-englerin
    Resumen: Modifications at the bridgehead position of englerin A were made to explore the effects of variation at this site on the molecule for biological activity, as judged by the NCI 60 screen, in which englerin A is highly potent and selective for renal cancer cells. Replacement of the isopropyl group by other, larger substituents yielded compounds which displayed excellent selectivity and potency comparable to the natural product. Selected compounds were also evaluated for their effect on the ion channel TRPC4 as well as for intravenous toxicity in mice, and these had lower potency in both assays compared to englerin A.
    Áreas temáticas: Química Organic chemistry Medicina ii Medicina i Materiais Interdisciplinar Farmacia Drug discovery Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Chemistry, medicinal Biotecnología Biochemistry
    Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
    Direcció de correo del autor: antoniomaria.echavarren@urv.cat
    Identificador del autor: 0000-0002-6418-7930
    Fecha de alta del registro: 2024-01-14
    Versión del articulo depositado: info:eu-repo/semantics/acceptedVersion
    Enlace a la fuente original: https://pubs.acs.org/doi/10.1021/acsmedchemlett.0c00186
    Referencia al articulo segun fuente origial: Acs Medicinal Chemistry Letters. 11 (9): 1711-1716
    Referencia de l'ítem segons les normes APA: Wu, Zhenhua; Suppo, Jean-Simon; Tumova, Sarka; Strope, Jonathan; Bravo, Fernando; Moy, Melody; Weinstein, Ethan S.; Peer, Cody J.; Figg, William D.; C (2020). Bridgehead Modifications of Englerin A Reduce TRPC4 Activity and Intravenous Toxicity but not Cell Growth Inhibition. Acs Medicinal Chemistry Letters, 11(9), 1711-1716. DOI: 10.1021/acsmedchemlett.0c00186
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    DOI del artículo: 10.1021/acsmedchemlett.0c00186
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2020
    Tipo de publicación: Journal Publications
  • Palabras clave:

    Biochemistry,Chemistry, Medicinal,Drug Discovery,Organic Chemistry
    Trpc4
    Tonantzitlolone
    Pkc-theta
    Mice
    Kidney cancer
    Ion channels
    Formal synthesis
    Englerin
    Cytotoxicity
    Channels
    Biological evaluation
    (-)-englerin
    Química
    Organic chemistry
    Medicina ii
    Medicina i
    Materiais
    Interdisciplinar
    Farmacia
    Drug discovery
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Chemistry, medicinal
    Biotecnología
    Biochemistry
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