title: Structure-activity relationship of Baifuzi-cerebrosides on BKCa channel activation.
abstract: Our previous study reported that a mixture of cerebrosides from traditional Chinese medicine Baifuzi could activate BKCa channel. It is curious to know the effect of each single cerebroside on the channel. Here we isolated 5 pure cerebrosides from the mixture and determined their chemical structures. The most potent one increased the single channel open probability 6 folds with EC50 value of 1.0 μM. The structure-activity relationship revealed that acyl chain length of cerebrosides has potent effect, while configuration of double bond at C8-C9 on their long chain base has weak effect on the channel activity. Thus, this research provides a guide for design and synthesis of a lead cerebroside with more potent effect on the BKCa channel.
authors.affiliation: Department of Basic Medical Sciences, Medical College of Xiamen University, Xiang'an Nan Lu, Xiamen 361102, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Basic Medical Sciences, Medical College of Xiamen University, Xiang'an Nan Lu, Xiamen 361102, China.
authors.forename: Yu-Jiao
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd, Hangzhou 310058, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Gao
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd, Hangzhou 310058, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ye
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd, Hangzhou 310058, China. Electronic address: qijianhua@zju.edu.cn.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Qi
authors.affiliation: Department of Basic Medical Sciences, Medical College of Xiamen University, Xiang'an Nan Lu, Xiamen 361102, China. Electronic address: qizhi@xmu.edu.cn.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Qi
mesh_terms: D000818:Animals; D016466:CHO Cells; D002554:Cerebrosides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D003412:Cricetulus; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D002554:Cerebrosides; D004365:Drugs, Chinese Herbal; D051036:Large-Conductance Calcium-Activated Potassium Channels
keywords: BK(Ca) channel; Baifuzi-cerebroside; Ischemic stroke