Synthesis of novel α-spinasterol derivatives and their inhibitory effects on CCL17 and CCL22 chemokine expression

Abstract

Natural α-spinasterol is well known for its various biological activities. In this study, we investigated the anti-inflammatory effects of newly synthesized α-spinasterol derivatives by tracking the expression of CCL17 and CCL22 chemokines, which serve as biomarkers for immune cell trafficking in skin inflammation. Initially, the 3-epimer of α-spinasterol, which results from inversion of stereochemistry at the C-3 position of α-spinasterol, was synthesized using the Mitsunobu reaction. Subsequently, new compounds were synthesized by introducing azido, amino, and amide groups at the C-3 position of α-spinasterol or 3-epi-α-spinasterol. The anti-inflammatory activity of these compounds was evaluated by examining their inhibitory effects on the mRNA expression of CCL17 and CCL22. Among these derivatives, 3α-8, 3α-12b, and 3α-12c exhibited potential anti-inflammatory activity in vitro, compared to α-spinasterol. Furthermore, compound 3α-8 showed even greater activity than 3α-12b and 3α-12c, underscoring its potential as a highly effective agent. These results suggest that the newly synthesized α-spinasterol derivatives hold promise as candidates for skin inflammation therapeutics.