Sipholane Triterpenoids: Chemistry, Reversal of ABCB1/P-Glycoprotein-Mediated Multidrug Resistance, and Pharmacophore Modeling
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- 作者：Sandeep Jain ; Ioana Abraham ; Paulo Carvalho ; Ye-Hong Kuang ; Lamiaa A. Shaala ; Diaa T. A. Youssef ; Mitchell A. Avery ; Zhe-Sheng Chen ; Khalid A. El Sayed
- 刊名：Journal of Natural Products
- 出版年：2009
- 出版时间：July 24, 2009
- 年：2009
- 卷：72
- 期：7
- 页码：1291-1298
- 全文大小：232K
- 年卷期：v.72,no.7(July 24, 2009)
- ISSN：1520-6025
文摘
This study reports the isolation of nine new terpenoids (2−10), possessing two novel skeletons, from the Red Sea sponge Callyspongia (=Siphonochalina) siphonella. The identity of these novel skeletons was based on X-ray crystallography and extensive spectral analyses. These compounds were evaluated for their ability to reverse P-glycoprotein (P-gp)-mediated multidrug resistance in human epidermoid cancer cells. Sipholenone E (3) was better than sipholenol A (1), a known P-gp modulator from this sponge, in reversing the P-gp-mediated multidrug resistance. Sipholenol L (6) and siphonellinol D (8) were nearly as active as sipholenol A. On the basis of X-ray crystallographic data and the established identity of 3−7, the structure of sipholenol I (11) is revised. A pharmacophore model of three hydrophobic points and two H-bond acceptors was generated for the active sipholane P-gp modulators.