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BAR502/fibrate conjugates: synthesis, biological evaluation and metabolic profile

dc.contributor.authorClaudia Finamore
dc.contributor.authorSimona De Marino
dc.contributor.authorChiara Cassiano
dc.contributor.authorGiuliano Napolitano
dc.contributor.authorPasquale Rapacciuolo
dc.contributor.authorSilvia Marchianò
dc.contributor.authorMichele Biagioli
dc.contributor.authorRosalinda Roselli
dc.contributor.authorCristina Di Giorgio
dc.contributor.authorCarmen Festa
dc.contributor.authorStefano Fiorucci
dc.contributor.authorAngela Zampella
dc.contributor.otherDepartment of Pharmacy, University of Naples, Naples, Italy
dc.contributor.otherDepartment of Pharmacy, University of Naples, Naples, Italy
dc.contributor.otherDepartment of Pharmacy, University of Naples, Naples, Italy
dc.contributor.otherDepartment of Pharmacy, University of Naples, Naples, Italy
dc.contributor.otherDepartment of Pharmacy, University of Naples, Naples, Italy
dc.contributor.otherDepartment of Medicine and Surgery, University of Perugia, Perugia, Italy
dc.contributor.otherDepartment of Medicine and Surgery, University of Perugia, Perugia, Italy
dc.contributor.otherDepartment of Medicine and Surgery, University of Perugia, Perugia, Italy
dc.contributor.otherDepartment of Medicine and Surgery, University of Perugia, Perugia, Italy
dc.contributor.otherDepartment of Pharmacy, University of Naples, Naples, Italy
dc.contributor.otherDepartment of Medicine and Surgery, University of Perugia, Perugia, Italy
dc.contributor.otherDepartment of Pharmacy, University of Naples, Naples, Italy
dc.date.accessioned2024-07-17T10:27:37Z
dc.date.accessioned2025-10-08T09:24:07Z
dc.date.available2025-10-08T09:24:07Z
dc.date.issued01-07-2024
dc.identifier.urihttp://digilib.fisipol.ugm.ac.id/repo/handle/15717717/40243
dc.description.abstractBAR502, a bile acid analogue, is active as dual FXR/GPBAR1 agonist and represents a promising lead for the treatment of cholestasis and NASH. In this paper we report the synthesis and the biological evaluation of a library of hybrid compounds prepared by combining, through high-yield condensation reaction, some fibrates with BAR502.The activity of the new conjugates was evaluated towards FXR, GPBAR1 and PPARα receptors, employing transactivation or cofactor recruitment assays. Compound 1 resulted as the most promising of the series and was subjected to further pharmacological investigation, together with stability evaluation and cell permeation assessment. We have proved by LCMS analysis that compound 1 is hydrolyzed in mice releasing clofibric acid and BAR505, the oxidized metabolite of BAR502, endowed with retained dual FXR/GPBAR1 activity.
dc.language.isoEN
dc.publisherFrontiers Media S.A.
dc.subject.lccChemistry
dc.titleBAR502/fibrate conjugates: synthesis, biological evaluation and metabolic profile
dc.typeArticle
dc.description.keywordshybrid prodrug
dc.description.keywordsBAR502
dc.description.keywordsfibrates
dc.description.keywordsbile acid receptors
dc.description.keywordsmetabolic profile
dc.description.keywordsstability
dc.description.doi10.3389/fchem.2024.1425867
dc.title.journalFrontiers in Chemistry
dc.identifier.e-issn2296-2646
dc.identifier.oaioai:doaj.org/journal:66a1ede6d3ce454db68ec5a259f39f5f


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