Linked Life Data

19637874

Source:http://linkedlifedata.com/resource/pubmed/id/19637874

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2010-6-21
pubmed:abstractText
It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
27
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5115-23
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Design and synthesis of novel C14-hydroxyl substituted triptolide derivatives as potential selective antitumor agents.
pubmed:affiliation
Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't