Synthesis and anti-inflammatory effects of Δ7-Cholestenol and Δ8(14)-Cholestenol derivatives

Abstract

In this study, O-glycosides of cholesterol derivatives Δ⁷-cholestenol and Δ⁸⁽¹⁴⁾-cholestenol were prepared by Schmidt glycosylation with various glycosyl imidates. In addition, 1,2,3-triazole-linked N-glycosides of Δ⁸⁽¹⁴⁾-cholestenol were prepared via the "click" reaction of proparzylic Δ⁸⁽¹⁴⁾-cholestenol with glycosyl azides. The anti-inflammatory activities of these molecules were investigated for inhibitory mRNA expression activity of CCL17 and CCL22, which are important biomarkers of atopic dermatitis. Both the O- and N-glycosides Δ⁷-cholestenol and Δ⁸⁽¹⁴⁾-cholestenol were observed to exhibit good anti-inflammatory activity in vitro. In particular, the 1,2,3-triazole-linked N-glycoside of Δ⁸⁽¹⁴⁾-cholestenol exhibited anti-inflammatory activity similar to that of O-glycoside in vitro and is expected to be more potent in vivo due to better stability.

Keywords: Anti-inflammatory; Chemokine; N-glycoside; Δ(7)-Cholestenol; Δ(8(14))-Cholestenol.