title: From taxuspine x to structurally simplified taxanes with remarkable p-glycoprotein inhibitory activity.
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.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Alcide de Gasperi 2, 53100 Siena, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Castagnolo
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Alcide de Gasperi 2, 53100 Siena, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Contemori
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Alcide de Gasperi 2, 53100 Siena, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Maccari
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Alcide de Gasperi 2, 53100 Siena, Italy.
authors.forename: Stanislava I
authors.initials: SI
authors.lastname: Avramova
authors.affiliation: Dipartimento di Neuroscienze, Università degli Studi di Siena, via A. Moro 2, 53100 Siena, Italy ; Istituto Toscano Tumori, via T. Alderotti 26N, 50139 Firenze, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Neri
authors.affiliation: Dipartimento di Neuroscienze, Università degli Studi di Siena, via A. Moro 2, 53100 Siena, Italy ; Istituto Toscano Tumori, via T. Alderotti 26N, 50139 Firenze, Italy.
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Sgaragli
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Alcide de Gasperi 2, 53100 Siena, Italy ; Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, BioLife Science Building, Suite 333, 1900 North 12th Street, Philadelphia, Pennsylvania 19122.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
keywords: MDR reversing agents; P-glycoprotein; Taxanes; macrolactone; non-natural natural product