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Avicholic Acid: A Lead Compound from Birds on the Route to Potent TGR5 Modulators.

ABSTRACT: Grounding on our former 3D QSAR studies, a knowledge-based screen of natural bile acids from diverse animal species has led to the identification of avicholic acid as a selective but weak TGR5 agonist. Chemical modifications of this compound resulted in the disclosure of 6?-ethyl-16-epi-avicholic acid that shows enhanced potency at TGR5 and FXR receptors. The synthesis, biological appraisals, and structure-activity relationships of this series of compounds are herein described. Moreover, a thorough physicochemical characterization of 6?-ethyl-16-epi-avicholic acid as compared to naturally occurring bile acids is reported and discussed.

SUBMITTER: Pellicciari R

PROVIDER: S-EPMC4025660 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Avicholic Acid: A Lead Compound from Birds on the Route to Potent TGR5 Modulators.

Pellicciari Roberto R Gioiello Antimo A Sabbatini Paola P Venturoni Francesco F Nuti Roberto R Colliva Carolina C Rizzo Giovanni G Adorini Luciano L Pruzanski Mark M Roda Aldo A Macchiarulo Antonio A

ACS medicinal chemistry letters 20120206 4

Grounding on our former 3D QSAR studies, a knowledge-based screen of natural bile acids from diverse animal species has led to the identification of avicholic acid as a selective but weak TGR5 agonist. Chemical modifications of this compound resulted in the disclosure of 6α-ethyl-16-epi-avicholic acid that shows enhanced potency at TGR5 and FXR receptors. The synthesis, biological appraisals, and structure-activity relationships of this series of compounds are herein described. Moreover, a thoro ...[more]

PMID: 24900463

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