From Taxuspine X to Structurally Simplified Taxanes with Remarkable P-Glycoprotein Inhibitory Activity

被引：7

作者：

Castagnolo, Daniele ^{[1
]}

Contemori, Lorenzo ^{[1
]}

Maccari, Giorgio ^{[1
]}

Avramova, Stanislava I. ^{[1
]}

Neri, Annalisa ^{[2
,3
]}

Sgaragli, Gianpietro ^{[2
,3
]}

Botta, Maurizio ^{[1
,4
]}

机构：

[1] Univ Siena, Dipartimento Farm Chim Tecnol, I-53100 Siena, Italy

[2] Univ Siena, Dipartimento Neurosci, I-53100 Siena, Italy

[3] Ist Toscano Tumori, I-50139 Florence, Italy

[4] Temple Univ, Coll Sci & Technol, Ctr Biotechnol, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2010年 / 1卷 / 08期

关键词：

Taxanes; MDR reversing agents; P-glycoprotein; macrolactone; non-natural natural product; RESISTANCE REVERSAL AGENTS; RING CLOSING METATHESIS; MULTIDRUG-RESISTANCE; BIOLOGICAL EVALUATION; ANTICANCER DRUG; NATURAL-PRODUCT; TAXOL; CANCER; BINDING; MACROCYCLIZATION;

D O I：

10.1021/ml100118k

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Three simplified non-natural natural taxanes, related to taxuspine x, were synthetized and assayed as p-glycoprotein (P-gp) inhibitors. One of them (6) proved to be a very efficient P-gp inhibitor with an IC50 = 7.2 x 10(-6) M. In addition, to rationalize biological data, a pharmacophoric model was built through a ligand-based approach. This model represents the first example of a pharmacophore, which describes interactions of taxanes with P-gp.

引用

页码：416 / 421

页数：6

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