Journal : Bioorg. Med. Chem. Lett.
Title : Design, synthesis and biological evaluation of bisabolangelone oxime derivatives as potassium-competitive acid blockers (P-CABs).
Year : 2016
Volume : 26
Issue : 9
First Page : 2268
Last Page : 2272
Authors : Huang NY, Wang WB, Chen L, Luo HJ, Wang JZ, Deng WQ, Zou K.
Abstract : 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 ΔGbind and pIC50 of ligands. Compound 5 exhibited the best inhibitory activity (pIC50=6.36) and most favorable binding free energy (ΔGbind=-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.