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Sipholane Triterpenoids: Chemistry, Reversal of ABCB1/P-Glycoprotein-Mediated Multidrug Resistance, and Pharmacophore Modeling

  作者 Jain, S; Abraham, I; Carvalho, P; Kuang, YH; Shaala, LA; Youssef, DTA; Avery, MA; Chen, ZS; El Sayed, KA  
  选自 期刊  Journal of natural products;  卷期  2009年72-7;  页码  1291-1298  
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[摘要]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 oil 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 1 (11) is revised. A pharmacophore model of three hydrophobic points and two H-bond acceptors was generated for the active sipholane P-gp modulators.

 
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