Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain

Archive ouverte

Gómez-Bouzó, Uxía | Peluso-Iltis, Carole | Santalla, Hugo | Quevedo, Mario Alfredo | Verlinden, Lieve | Verstuyf, Annemieke | Fall, Yagamare | Gómez, Generosa | Rochel, Natacha

Edité par CCSD ; American Chemical Society -

International audience. 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.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion