Stereoisomerization of human constitutive androstane receptor agonist CITCO

Diethelm-Varela, Benjamin; Kumar, Anmol; Lynch, Caitlin; Imler, Gregory H.; Deschamps, Jeffrey R.; Li, Yue; Xia, Menghang; MacKerell, Alexander D., Jr.; Xue, Fengtian


CITCO (6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl) oxime) is a widely used agonist of the human constitutive androstane receptor (hCAR), a key hepatic xenobiotic sensor protein with emerging therapeutic indications. To address the insufficient stability of CITCO, which limits its therapeutic potential, the E- and Z-isomers of CITCO were synthesized and characterized by X-ray crystallography, one- and two-dimensional NMR spectroscopy. The two isomers were found to undergo E/Z isomerizations in solution likely via a protonation-rotation mechanism, time- and concentration-dependently. Our molecular modeling studies suggests both stereoisomers can bind to hCAR. (C) 2020 Elsevier Ltd. All rights reserved.

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Título según WOS: ID WOS:000604923900030 Not found in local WOS DB
Título de la Revista: TETRAHEDRON
Volumen: 79
Fecha de publicación: 2021


Notas: ISI