title: Structure-based discovery of potassium channel blockers from natural products: virtual screening and electrophysiological assay testing.
abstract: Potassium ion (K(+)) channels are attractive targets for rational drug design. Based upon a three-dimensional model of the eukaryotic K(+) channels, the docking virtual screening approach was employed to search the China Natural Products Database. Compounds were ranked according to the relative binding energy, favorable shape complementarity, and potential of forming hydrogen bonds with the K(+) channel. Four candidate compounds found by virtual screening were investigated by using the whole-cell voltage-clamp recording in rat dissociated hippocampal neurons. When applied extracellularly, compound 1 markedly depressed the delayed rectifier K(+) current (I(K)) and fast transient K(+) current (I(A)), whereas compounds 2, 3, and 4 exerted a more potent and selective inhibitory effect on I(K). Intracellular application of the four compounds had no effect on both the K(+) currents.
authors.affiliation: Center for Drug Discovery and Design, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 201203, Shanghai, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Mingke
authors.initials: M
authors.lastname: Song
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Tan
authors.forename: Feng
authors.initials: F
authors.lastname: Cheng
authors.forename: Suxin
authors.initials: S
authors.lastname: Zheng
authors.forename: Jianhua
authors.initials: J
authors.lastname: Shen
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Luo
authors.forename: Ruyun
authors.initials: R
authors.lastname: Ji
authors.forename: Jianmin
authors.initials: J
authors.lastname: Yue
authors.forename: Guoyuan
authors.initials: G
authors.lastname: Hu
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Kaixian
authors.initials: K
authors.lastname: Chen
mesh_terms: D000818:Animals; D001665:Binding Sites; D001688:Biological Products / Q000737:chemistry*; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D015221:Potassium Channels; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D026902:Potassium Channel Blockers; D015221:Potassium Channels