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

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Pellicciari R, Gioiello A, Sabbatini P, Venturoni F, Nuti R, Colliva C, Rizzo G, Adorini L, Pruzanski M, Roda A, Macchiarulo A

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

ACS Med Chem Lett. 2012 Feb 6;3(4):273-7. doi: 10.1021/ml200256d. eCollection 2012 Apr 12.

PubMed ID

24900463 [ View in PubMed

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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 6alpha-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 6alpha-ethyl-16-epi-avicholic acid as compared to naturally occurring bile acids is reported and discussed.