title: Structure-cardiac activity relationship of C19-diterpenoid alkaloids.
abstract: Thirty three C19-diterpenoid alkaloids, twenty-two prepared from known C19-diterpenoid alkaloids and eleven isolated from Aconitum and Delphinium spp. were evaluated for their cardiac activity in the isolated bullfrog heart assay. Among them, eleven compounds exhibited cardiac activity, with average rate of amplitude increase in the range of 16-118%. Compound 7, mesaconine (17), hypaconine (25), and beiwutinine (26) exhibited strong cardiac activities relative to the reference drug. The structure-activity relationship data acquired indicated that an alpha-hydroxyl group at C-15, a hydroxyl group at C-8, an alpha-methoxyl or hydroxyl group at C-1, and a secondary amine or N-methyl group in ring A are important structure features necessary for the cardiac activities of the aconitine-type C19-diterpenoid alkaloids without any ester groups. In addition, an alpha-hydroxyl group at C-3 is also helpful for the cardiac activity of these alkaloids.
authors: Department of Chemistry of Medicinal Natural Products, West China College of Pharmacy, Sichuan University, Chengdu, Sichuan, PR China 610041.
authors: Xi-Xian
authors: XX
authors: Jian
authors: Pei
authors: P
authors: Tang
authors: Xiu-Xiu
authors: XX
authors: Liu
authors: Ruo-Bing
authors: RB
authors: Chao
authors: Qiao-Hong
authors: QH
authors: Chen
authors: Xue-Ke
authors: XK
authors: She
authors: Dong-Lin
authors: DL
authors: Chen
authors: Feng-Peng
authors: FP
authors: Wang
mesh_terms: D031841:Aconitum / Q000737:chemistry; D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D031882:Delphinium / Q000737:chemistry; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D011892:Rana catesbeiana; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D004224:Diterpenes