Proteasome Inhibitors from Neoboutonia melleri
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- 作者：Christophe Long ; Jos茅phine Beck ; Fr茅d茅ric Cantagrel ; Laurence Marcourt ; Laure Vendier ; Bruno David ; Fabien Plisson ; Fadila Derguini ; Isabelle Vandenberghe ; Yannick Aussagues ; Fr茅d茅ric Ausseil ; Catherine Lavaud ; Fran莽ois Sautel ; Georges Massiot
- 刊名：Journal of Natural Products
- 出版年：2012
- 出版时间：January 27, 2012
- 年：2012
- 卷：75
- 期：1
- 页码：34-47
- 全文大小：426K
- 年卷期：v.75,no.1(January 27, 2012)
- ISSN：1520-6025
文摘
Thirty new cycloartane derivatives (1鈥?b>3, 5鈥?b>12, 14鈥?b>32) have been isolated from the leaves of Neoboutonia melleri. Their novelty stems from the loss of one of the C-4 methyl groups (1鈥?b>3, 5鈥?b>12, 14鈥?b>25, and 32) and from the presence of an 鈥渆xtra鈥?carbon atom in the side chain (1鈥?b>3, 5鈥?b>12, 14鈥?b>20, 26鈥?b>29, and 30鈥?b>32). Furthermore, compound 32 possesses a rare triterpene skeleton with the cyclopropane ring fused onto C-1 and C-10, instead of C-9 and C-10. The structures were determined by spectrometric means, chemical correlations, and X-ray crystallography of derivative 1c. The substitution pattern in ring A, with a cyclopropyl ring conjugated with an 伪,尾-unsaturated carbonyl moiety, confers to the molecule a particular reactivity, giving rise to a formal inversion of the stereochemistry of the cyclopropane ring under UV irradiation. These compounds showed an interesting level of activity on the proteasome pathway, thus motivating their evaluation as possible anticancer agents. The large number of isolated compounds permitted a structure鈥揳ctivity relationship analysis, which showed that the presence of the two enone functions was a requirement for the activity.