Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain
Abstract
We synthesized two new gemini analogues UG-480 and UG-481 that incorporate a modified longer side chain containing a cyclopropane group. The evaluation of the bioactivities of the two gemini analogues indicated that the 17,20 threo (20S) compound, UG-480, is the most active one and as active as 1,25(OH)2D3. Docking and MD data showed that the compounds bind efficiently to VDR with UG-480 forming an energetically more favorable interaction with His397. Structural analysis indicated that whereas the UG-480 compound efficiently stabilizes the active VDR conformation, it induces conformational changes in H6-H7 VDR region that are greater than those induced by the parental Gemini and that this is due to the occupancy of the secondary channel by its modified side chain.
Domains
Life Sciences [q-bio]| Origin | Files produced by the author(s) |
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