Design, synthesis and structure-activity relationships of novel taxane-based multidrug resistance reversal agents

Iwao Ojima; Christopher P. Borella; Xinyuan Wu; Pierre Yves Bounaud; Cecilia Fumero Oderda; Matthew Sturm; Michael L. Miller; Subrata Chakravarty; Jin Chen; Qing Huang; Paula Pera; Tracy A. Brooks; Maria R. Baer; Ralph J. Bernacki

doi:10.1021/jm049483y

Design, synthesis and structure-activity relationships of novel taxane-based multidrug resistance reversal agents

Iwao Ojima
, Christopher P. Borella
, Xinyuan Wu
, Pierre Yves Bounaud
, Cecilia Fumero Oderda
, Matthew Sturm
, Michael L. Miller
, Subrata Chakravarty
, Jin Chen
, Qing Huang
, Paula Pera
, Tracy A. Brooks
, Maria R. Baer
, Ralph J. Bernacki

Chemistry

Stony Brook University
Roswell Park Cancer Institute

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

44 Scopus citations

Abstract

A series of novel taxane-based multidrug resistance (MDR) reversal agents (TRAs) has been designed and synthesized. Structure - activity relationship (SAR) study clearly indicates that modification of the C-7 position with hydrophobic arenecarbonylcinnamoyl groups brings about high potency against drug efflux mediated by P-glycoprotein (P-gp). Six TRAs exhibit ability to modulate a wide range of ATP-binding cassette (ABC) transporters, such as P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which may serve as novel broad-spectrum modulators of ABC transporters.

Original language	English
Pages (from-to)	2218-2228
Number of pages	11
Journal	Journal of Medicinal Chemistry
Volume	48
Issue number	6
DOIs	https://doi.org/10.1021/jm049483y
State	Published - Mar 24 2005

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Ojima, I., Borella, C. P., Wu, X., Bounaud, P. Y., Oderda, C. F., Sturm, M., Miller, M. L., Chakravarty, S., Chen, J., Huang, Q., Pera, P., Brooks, T. A., Baer, M. R., & Bernacki, R. J. (2005). Design, synthesis and structure-activity relationships of novel taxane-based multidrug resistance reversal agents. Journal of Medicinal Chemistry, 48(6), 2218-2228. https://doi.org/10.1021/jm049483y

@article{2a25575af0734b58b99f591400947583,

title = "Design, synthesis and structure-activity relationships of novel taxane-based multidrug resistance reversal agents",

abstract = "A series of novel taxane-based multidrug resistance (MDR) reversal agents (TRAs) has been designed and synthesized. Structure - activity relationship (SAR) study clearly indicates that modification of the C-7 position with hydrophobic arenecarbonylcinnamoyl groups brings about high potency against drug efflux mediated by P-glycoprotein (P-gp). Six TRAs exhibit ability to modulate a wide range of ATP-binding cassette (ABC) transporters, such as P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which may serve as novel broad-spectrum modulators of ABC transporters.",

author = "Iwao Ojima and Borella, \{Christopher P.\} and Xinyuan Wu and Bounaud, \{Pierre Yves\} and Oderda, \{Cecilia Fumero\} and Matthew Sturm and Miller, \{Michael L.\} and Subrata Chakravarty and Jin Chen and Qing Huang and Paula Pera and Brooks, \{Tracy A.\} and Baer, \{Maria R.\} and Bernacki, \{Ralph J.\}",

year = "2005",

month = mar,

day = "24",

doi = "10.1021/jm049483y",

language = "English",

volume = "48",

pages = "2218--2228",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

number = "6",

}

Ojima, I, Borella, CP, Wu, X, Bounaud, PY, Oderda, CF, Sturm, M, Miller, ML, Chakravarty, S, Chen, J, Huang, Q, Pera, P, Brooks, TA, Baer, MR & Bernacki, RJ 2005, 'Design, synthesis and structure-activity relationships of novel taxane-based multidrug resistance reversal agents', Journal of Medicinal Chemistry, vol. 48, no. 6, pp. 2218-2228. https://doi.org/10.1021/jm049483y

TY - JOUR

T1 - Design, synthesis and structure-activity relationships of novel taxane-based multidrug resistance reversal agents

AU - Ojima, Iwao

AU - Borella, Christopher P.

AU - Wu, Xinyuan

AU - Bounaud, Pierre Yves

AU - Oderda, Cecilia Fumero

AU - Sturm, Matthew

AU - Miller, Michael L.

AU - Chakravarty, Subrata

AU - Chen, Jin

AU - Huang, Qing

AU - Pera, Paula

AU - Brooks, Tracy A.

AU - Baer, Maria R.

AU - Bernacki, Ralph J.

PY - 2005/3/24

Y1 - 2005/3/24

N2 - A series of novel taxane-based multidrug resistance (MDR) reversal agents (TRAs) has been designed and synthesized. Structure - activity relationship (SAR) study clearly indicates that modification of the C-7 position with hydrophobic arenecarbonylcinnamoyl groups brings about high potency against drug efflux mediated by P-glycoprotein (P-gp). Six TRAs exhibit ability to modulate a wide range of ATP-binding cassette (ABC) transporters, such as P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which may serve as novel broad-spectrum modulators of ABC transporters.

AB - A series of novel taxane-based multidrug resistance (MDR) reversal agents (TRAs) has been designed and synthesized. Structure - activity relationship (SAR) study clearly indicates that modification of the C-7 position with hydrophobic arenecarbonylcinnamoyl groups brings about high potency against drug efflux mediated by P-glycoprotein (P-gp). Six TRAs exhibit ability to modulate a wide range of ATP-binding cassette (ABC) transporters, such as P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which may serve as novel broad-spectrum modulators of ABC transporters.

UR - https://www.scopus.com/pages/publications/20144384731

U2 - 10.1021/jm049483y

DO - 10.1021/jm049483y

M3 - Article

C2 - 15771464

AN - SCOPUS:20144384731

SN - 0022-2623

VL - 48

SP - 2218

EP - 2228

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 6

ER -

Design, synthesis and structure-activity relationships of novel taxane-based multidrug resistance reversal agents

Abstract

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