title: Further Studies on Structure-Cardiac Activity Relationships of Diterpenoid Alkaloids.
abstract: The cardiac effect of thirty-eight diterpenoid alkaloids was evaluated on the isolated bullfrog heart model. Among them, twelve compounds exhibited appreciable cardiac activity, with compounds 3 and 35 being more active than the reference drug lanatoside. The structure-cardiac activity relationships of the diterpenoid alkaloids were summarized based on our present and previous studies [2]: i) 1α-OMe or 1α-OH, 8-OH, 14-OH, and NH (or NMe) are key structural features important for the cardiac effect of the aconitine-type C19-diterpenoid alkaloids without any esters. C18-diterpenoid alkaloids, lycoctonine-type C19-diterpenoid alkaloids, and the veatchine- and denudatine-type C20-diterpenoid alkaloids did not show any cardiac activity; ii) the presence of 3α-OH is beneficial to the cardiac activity; iii) the effect on the cardiac action of 6α-OMe, 13-OH, 15α-OH, and 16-demethoxy or a double bond between C-15 and C-16 depends on the substituent pattern on the nitrogen atom.
authors.forename: Zhong-Tang
authors.initials: ZT
authors.lastname: Zhang
authors.forename: Xi-Xian
authors.initials: XX
authors.lastname: Jian
authors.forename: Jia-Yu
authors.initials: JY
authors.lastname: Ding
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Deng
authors.forename: Ruo-Bing
authors.initials: RB
authors.lastname: Chao
authors.forename: Qiao-Hong
authors.initials: QH
authors.lastname: Chen
authors.forename: Dong-Lin
authors.initials: DL
authors.lastname: Chen
authors.forename: Feng-Peng
authors.initials: FP
authors.lastname: Wang
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002317:Cardiovascular Agents / Q000737:chemistry / Q000494:pharmacology*; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D015394:Molecular Structure; D011892:Rana catesbeiana; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D002317:Cardiovascular Agents; D004224:Diterpenes