Modification in the side chain of solomonsterol A: discovery of cholestan disulfate as a potent pregnane-X-receptor agonist.

摘要: Seven synthetic analogues of the PXR (pregnane-X-receptor) potent natural agonist solomonsterol A were prepared by total synthesis. Their activity toward was assessed transactivation and RT-PCR assays. The study discloses cholestan disulfate (8) as a new, simplified PXR. By in vitro studies on hepatic cells we have demonstrated that this compound is functional characterization human macrophages stellate provided evidence has ability to modulate immune response triggered bacterial endotoxin well counter-activate cell activation induced thrombin. Because inhibition immune-driven circuits might relevance treatment inflammation liver fibrosis, present data support development preclinical models inflammatory diseases.