Design, synthesis and biological evaluation of bisabolangelone oxime derivatives as potassium-competitive acid blockers (P-CABs)

摘要

With the aim of searching novel P-CABs, seven bisabolangelone oxime derivatives were designed, synthesized, characterized and evaluated the H+, K+-ATPase inhibitory activities guided by computer aided drug design methods. The binding free energy calculations were in good agreement with the experiment results with the correlation coefficient R of -0.9104 between Delta G(bind) and pIC(50) of ligands. Compound 5 exhibited the best inhibitory activity (pIC(50) = 6.36) and most favorable binding free energy (DGbind = -47.67 kcal/mol) than other derivatives. The binding sites of these compounds were found to be the hydrophobic substituted groups with the Cys813 residue by the decomposed binding free energy analysis. (C) 2016 Elsevier Ltd. All rights reserved.