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Published on: November 15, 2013
Side-Chain Modified Ergosterol and Stigmasterol Derivatives as Liver X Receptor Agonists
Maura Marinozzi1, Francisco Fermin Castro Navas1, Daniela Maggioni2
1Dipartimento di Scienze Farmaceutiche, Università degli Studi di Perugia , Via del Liceo, 1-06123 Perugia, Italy.
Abstract:
A series of stigmasterol and ergosterol derivatives, characterized by the presence of oxygenated functions at C-22 and/or C-23 positions, were designed as potential liver X receptor (LXR) agonists. The absolute configuration of the newly created chiral centers was definitively assigned for all the corresponding compounds. Among the 16 synthesized compounds, 21, 27, and 28 were found to be selective LXRα agonists, whereas 20, 22, and 25 showed good selectivity for the LXRβ isoform. In particular, 25 showed the same degree of potency as 22R-HC (3) at LXRβ, while it was virtually inactive at LXRα (EC50 = 14.51 μM). Interestingly, 13, 19, 20, and 25 showed to be LXR target gene-selective modulators, by strongly inducing the expression of ABCA1, while poorly or not activating the lipogenic genes SREBP1 and SCD1 or FASN, respectively.
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