کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1361522 | 981466 | 2008 | 14 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Co-existence of α-glucosidase-inhibitory and liver X receptor-regulatory activities and their separation by structural development Co-existence of α-glucosidase-inhibitory and liver X receptor-regulatory activities and their separation by structural development](/preview/png/1361522.png)
Liver X receptors (LXR), which were originally reported as oxysterol-activated nuclear receptors, were recently found to recognize glucose as a physiological ligand. On this basis, we have already developed novel LXR antagonists based upon α-glucosidase inhibitors derived from thalidomide. Here, to clarify the relationship between α-glucosidase inhibition and LXR modulation, we investigate the α-glucosidase-inhibitory activity of typical LXR ligands and the LXR-modulating activity of typical α-glucosidase inhibitors. Although there were some exceptions, co-existence of LXR-regulatory and α-glucosidase-inhibitory activities seemed to be rather general among the examined compounds. The LXR ligands were found to be non-competitive α-glucosidase inhibitors, suggesting that it might be possible to separate the two activities. To test this idea, we focused on riccardin C, a naturally occurring LXR ligand, which we found here to be a potent α-glucosidase inhibitor as well. Structural development of riccardin C afforded novel LXR antagonists lacking α-glucosidase-inhibitory activity, 19c and 19f, and a LXRα-selective antagonist, 22.
Some typical LXR ligands and α-glucosidase inhibitors were found to possess α-glucosidase-inhibitory activity and LXR-antagonistic activity, respectively. The dual activity elicited by riccardin was seperated by its structural development.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 8, 15 April 2008, Pages 4272–4285