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

doi:10.1016/j.bmcl.2016.03.051

	Design, synthesis and biological evaluation of bisabolangelone oxime derivatives as potassium-competitive acid blockers (P-CABs)
	Wang, Wen-Bin 1; Huang, Nian-Yu 1; Chen, Lei 1; Luo, Hua-Jun 1; Wang, Jun-Zhi 1; Deng, Wei-Qiao 2; Zou, Kun 1
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2016-05-01
卷号	26 期号:9 页码:2268-2272
关键词	P-cabs Bisabolangelone Drug Rational Design Synthesis H++ k+-atpase Inhibitory Activities
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2016.03.051
文献子类	Article
英文摘要	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.
WOS关键词	INDUCED-FIT DOCKING ; GASTRIC H,K-ATPASE ; DRUG TARGET ; ATPASE ; H+,K+-ATPASE ; INHIBITORS ; BINDING ; MECHANICS ; LOOP
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000373739700033
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/170740]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Luo, Hua-Jun
作者单位	1.China Three Gorges Univ, Coll Biol & Pharmaceut Sci, Hubei Key Lab Nat Prod Res & Dev, Yichang 443002, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian Natl Lab Clean Energy, State Key Lab Mol React Dynam, 457 Zhongshan Rd, Dalian 116023, Peoples R China
推荐引用方式 GB/T 7714	Wang, Wen-Bin,Huang, Nian-Yu,Chen, Lei,et al. Design, synthesis and biological evaluation of bisabolangelone oxime derivatives as potassium-competitive acid blockers (P-CABs)[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2016,26(9):2268-2272.
APA	Wang, Wen-Bin.,Huang, Nian-Yu.,Chen, Lei.,Luo, Hua-Jun.,Wang, Jun-Zhi.,...&Zou, Kun.(2016).Design, synthesis and biological evaluation of bisabolangelone oxime derivatives as potassium-competitive acid blockers (P-CABs).BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,26(9),2268-2272.
MLA	Wang, Wen-Bin,et al."Design, synthesis and biological evaluation of bisabolangelone oxime derivatives as potassium-competitive acid blockers (P-CABs)".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 26.9(2016):2268-2272.