Structure-Analgesic Activity Relationship Studies on the C-18- and C-19-Diterpenoid Alkaloids

doi:10.1248/cpb.57.801

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第二研究室

	Structure-Analgesic Activity Relationship Studies on the C-18- and C-19-Diterpenoid Alkaloids
	Wang, Jian-Li 1; Shen, Xiang-Li 2; Chen, Qiao-Hong 1; Qi, Gong 3; Wang, Wei 3; Wang, Feng-Peng 1
刊名	CHEMICAL & PHARMACEUTICAL BULLETIN
	2009-08
卷号	57 期号:8 页码:801-807
关键词	diterpenoid alkaloid lappaconitine crassicauline A yunaconitine analgesic activity
ISSN号	0009-2363
DOI	10.1248/cpb.57.801
文献子类	Article
英文摘要	For evaluation of C-18- and C-19-diterpenoid alkaloids as analgesics, three C-19-diterpenoid alkaloids were isolated from the roots of Aconitum hemsleyanum var. circinatum and A. transsecutum; and twenty-five semisynthetic C-18- or C-19-diterpenoid alkaloids were prepared from lappaconitine, crassicauline A or yunaconitine. In a mice acetic acid-induced abdominal constriction assay, four crassicauline A analogs and three yunaconitine analogs exhibited good analgesic activities with 77.8-94.1% inhibition range in 0.1-10 mg/kg subcutaneous (s.c.) dose range at the point of 20 min after drug administration. Among them, 8-O-deacetyl-8-O-ethylcrassicauline A (ED50=0.0972 mg/kg) and 8-O-ethylyunaconitine (ED50=0.0591 mg/kg) were the most potent analgesics relative to the reference drugs lappaconitine (ED50=3.50 mg/kg) and crassicauline A (ED50=0.0480 mg/kg). Analgesic activity data of these C-18- and C-19-diterpenoid alkaloids indicate that a tertiary amine in ring A, an acetoxyl or an ethoxyl group at C-8, an aromatic ester at C-14, and the saturation state of the ring D are important structural features necessary to the analgesic activity of the C-19-diterpenoid alkaloids.
资助项目	National Natural Science Foundation of China[30672526]
WOS关键词	NORDITERPENOID ALKALOIDS ; N-DEACETYLLAPPACONITINE ; LAPPACONITINE ; JESACONITINE ; DERIVATIVES
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PHARMACEUTICAL SOC JAPAN
WOS记录号	WOS:000268547300003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279172]
专题	药理学第二研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Wang, Feng-Peng
作者单位	1.Sichuan Univ, Dept Chem Med Nat Prod, Chengdu 610041, Peoples R China; 2.Sichuan Univ, W China Hosp 2, Chengdu 610041, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Jian-Li,Shen, Xiang-Li,Chen, Qiao-Hong,et al. Structure-Analgesic Activity Relationship Studies on the C-18- and C-19-Diterpenoid Alkaloids[J]. CHEMICAL & PHARMACEUTICAL BULLETIN,2009,57(8):801-807.
APA	Wang, Jian-Li,Shen, Xiang-Li,Chen, Qiao-Hong,Qi, Gong,Wang, Wei,&Wang, Feng-Peng.(2009).Structure-Analgesic Activity Relationship Studies on the C-18- and C-19-Diterpenoid Alkaloids.CHEMICAL & PHARMACEUTICAL BULLETIN,57(8),801-807.
MLA	Wang, Jian-Li,et al."Structure-Analgesic Activity Relationship Studies on the C-18- and C-19-Diterpenoid Alkaloids".CHEMICAL & PHARMACEUTICAL BULLETIN 57.8(2009):801-807.