From taxuspine X to structurally simplified taxanes with remarkable P-Glycoprotein inhibitory activity

Daniele Castagnolo; Lorenzo Contemori; Giorgio Maccari; Stanislava Avramova; Annalisa Neri; Gianpietro Sgaragli; Maurizio Botta

doi:10.1021/ml100118k

From taxuspine X to structurally simplified taxanes with remarkable P-Glycoprotein inhibitory activity

Daniele Castagnolo, Lorenzo Contemori, Giorgio Maccari, Stanislava Avramova, Annalisa Neri, Gianpietro Sgaragli, Maurizio Botta

Northumbria University

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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.

Original language	English
Pages (from-to)	416-421
Journal	ACS Medicinal Chemistry Letters
Volume	1
Issue number	8
DOIs	https://doi.org/10.1021/ml100118k
Publication status	Published - 2010

Keywords

taxanes
MDR reversing agents
P-glycoprotein
macrolactone
non-natural natural product

Access to Document

10.1021/ml100118k

Cite this

@article{d76db9724ea549938d29be42a160ae9e,

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.",

keywords = "taxanes, MDR reversing agents, P-glycoprotein, macrolactone, non-natural natural product",

author = "Daniele Castagnolo and Lorenzo Contemori and Giorgio Maccari and Stanislava Avramova and Annalisa Neri and Gianpietro Sgaragli and Maurizio Botta",

year = "2010",

doi = "10.1021/ml100118k",

language = "English",

volume = "1",

pages = "416--421",

journal = "ACS Medicinal Chemistry Letters",

issn = "1948-5875",

publisher = "American Chemical Society",

number = "8",

}

TY - JOUR

T1 - From taxuspine X to structurally simplified taxanes with remarkable P-Glycoprotein inhibitory activity

AU - Castagnolo, Daniele

AU - Contemori, Lorenzo

AU - Maccari, Giorgio

AU - Avramova, Stanislava

AU - Neri, Annalisa

AU - Sgaragli, Gianpietro

AU - Botta, Maurizio

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - taxanes

KW - MDR reversing agents

KW - P-glycoprotein

KW - macrolactone

KW - non-natural natural product

UR - https://www.scopus.com/pages/publications/78649301900

U2 - 10.1021/ml100118k

DO - 10.1021/ml100118k

M3 - Article

SN - 1948-5875

VL - 1

SP - 416

EP - 421

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 8

ER -

From taxuspine X to structurally simplified taxanes with remarkable P-Glycoprotein inhibitory activity

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this