title: Conicasterol E, a small heterodimer partner sparing farnesoid X receptor modulator endowed with a pregnane X receptor agonistic activity, from the marine sponge Theonella swinhoei.
abstract: We report the isolation and pharmacological characterization of conicasterol E isolated from the marine sponge Theonella swinhoei. Pharmacological characterization of this steroid in comparison to CDCA, a natural FXR ligand, and 6-ECDCA, a synthetic FXR agonist generated by an improved synthetic strategy, and rifaximin, a potent PXR agonist, demonstrated that conicasterol E is an FXR modulator endowed with PXR agonistic activity. Conicasterol E induces the expression of genes involved in bile acids detoxification without effect on the expression of small heterodimer partner (SHP), thus sparing the expression of genes involved in bile acids biosynthesis. The relative positioning in the ligand binding domain of FXR, explored through docking calculations, demonstrated a different spatial arrangement for conicasterol E and pointed to the presence of simultaneous and efficient interactions with the receptor. In summary, conicasterol E represents a FXR modulator and PXR agonist that might hold utility in treatment of liver disorders.
authors: Dipartimento di Chimica delle Sostanze Naturali, Università di Napoli "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
authors: Valentina
authors: V
authors: Sepe
authors: Raffaella
authors: R
authors: Ummarino
authors: Maria Valeria
authors: MV
authors: D'Auria
authors: Maria Giovanna
authors: MG
authors: Chini
authors: Giuseppe
authors: G
authors: Bifulco
authors: Barbara
authors: B
authors: Renga
authors: Claudio
authors: C
authors: D'Amore
authors: Cécile
authors: C
authors: Debitus
authors: Stefano
authors: S
authors: Fiorucci
authors: Angela
authors: A
authors: Zampella
mesh_terms: D000818:Animals; D059001:Aquatic Organisms; D001647:Bile Acids and Salts / Q000378:metabolism; D001665:Binding Sites; D045744:Cell Line, Tumor; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D011987:Receptors, Steroid / Q000819:agonists* / Q000737:chemistry; D012294:Rifamycins / Q000494:pharmacology; D000078262:Rifaximin; D047232:Theonella / Q000737:chemistry*; D015533:Transcriptional Activation / Q000187:drug effects; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D002784:Cholesterol; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D012294:Rifamycins; D000078262:Rifaximin; D000099150:Receptor, Farnesoid X-Activated; C570906:conicasterol E; C464660:obeticholic acid