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From taxuspine x to structurally simplified taxanes with remarkable p-glycoprotein inhibitory activity
Daniele Castagnolo1, Lorenzo Contemori1, Giorgio Maccari1
1Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Alcide de Gasperi 2, 53100 Siena, Italy.
Abstract:
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 × 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.
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