Source:http://linkedlifedata.com/resource/pubmed/id/11063620
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
22
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pubmed:dateCreated |
2000-11-20
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pubmed:abstractText |
We have designed and synthesized 16 new olean- and urs-1-en-3-one triterpenoids with various modified rings C as potential antiinflammatory and cancer chemopreventive agents and evaluated their inhibitory activities against production of nitric oxide induced by interferon-gamma in mouse macrophages. This investigation revealed that 9(11)-en-12-one and 12-en-11-one functionalities in ring C increase the potency by about 2-10 times compared with the original 12-ene. Subsequently, we have designed and synthesized novel olean- and urs-1-en-3-one derivatives with nitrile and carboxyl groups at C-2 in ring A and with 9(11)-en-12-one and 12-en-11-one functionalities in ring C. Among them, we have found that methyl 2-cyano-3, 12-dioxooleana-1,9(11)-dien-28-oate (25), 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) (26), and methyl 2-carboxy-3,12-dioxooleana-1,9(11)-dien-28-oate (29) have extremely high potency (IC(50) = 0.1 nM level). Their potency is similar to that of dexamethasone although they do not act through the glucocorticoid receptor. Overall, the combination of modified rings A and C increases the potency by about 10 000 times compared with the lead compound, 3-oxooleana-1,12-dien-28-oic acid (8) (IC(50) = 1 microM level). The selected oleanane triterpenoid, CDDO (26), was found to be a potent, multifunctional agent in various in vitro assays and to show antiinflammatory activity against thioglycollate-interferon-gamma-induced mouse peritonitis.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-cyano-3,12-dioxoolean-1,9-dien-28-...,
http://linkedlifedata.com/resource/pubmed/chemical/2-mercaptoacetate,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Oleanolic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Thioglycolates,
http://linkedlifedata.com/resource/pubmed/chemical/Triterpenes
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
2
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4233-46
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11063620-Animals,
pubmed-meshheading:11063620-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:11063620-Antineoplastic Agents,
pubmed-meshheading:11063620-Cells, Cultured,
pubmed-meshheading:11063620-Female,
pubmed-meshheading:11063620-Interferon-gamma,
pubmed-meshheading:11063620-Macrophages, Peritoneal,
pubmed-meshheading:11063620-Mice,
pubmed-meshheading:11063620-Nitric Oxide,
pubmed-meshheading:11063620-Oleanolic Acid,
pubmed-meshheading:11063620-Peritonitis,
pubmed-meshheading:11063620-Structure-Activity Relationship,
pubmed-meshheading:11063620-Thioglycolates,
pubmed-meshheading:11063620-Triterpenes
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pubmed:year |
2000
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pubmed:articleTitle |
Synthetic oleanane and ursane triterpenoids with modified rings A and C: a series of highly active inhibitors of nitric oxide production in mouse macrophages.
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pubmed:affiliation |
Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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