New Synthetic Triterpenoids: Potent Agents for Prevention and Treatment of Tissue Injury Caused by Inflammatory and Oxidative Stress

详细信息    查看全文

• 作者：Michael B. Sporn ; Karen T. Liby ; Mark M. Yore ; Liangfeng Fu ; Justin M. Lopchuk ; Gordon W. Gribble
• 刊名：Journal of Natural Products
• 出版年：2011
• 出版时间：March 25, 2011
• 年：2011
• 卷：74
• 期：3
• 页码：537-545
• 全文大小：1047K
• 年卷期：v.74,no.3(March 25, 2011)
• ISSN：1520-6025

文摘

We review the original rationale for the development and the chemistry of a series of new synthetic oleanane triterpenoids (SO), based on oleanolic acid (<b>1b>) as a starting material. Many of the new compounds that have been made, such as 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (鈥淐DDO鈥? <b>8b>), are highly potent (activities found at levels below 1 nM) anti-inflammatory agents, as measured by their ability to block the cellular synthesis of the enzyme inducible nitric oxide synthase (iNOS) in activated macrophages. Details of the organic synthesis of new SO and their chemical mechanisms of biological activity are reviewed, as is formation of biotin conjugates for investigation of protein targets. Finally, we give a brief summary of important biological activities of SO in many organ systems in numerous animal models. Clinical investigation of a new SO (methyl 2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate, 鈥淐DDO-Me鈥? bardoxolone methyl, <b>13b>) is currently in progress.