Synthesis and evaluation of nitric oxide-releasing DDB derivatives as potential Pgp-mediated MDR reversal agents in MCF-7/Adr cells

Xiaobo Tang; Xiaoke Gu; Hua Ai; Guangji Wang; Hui Peng; Yisheng Lai; Yihua Zhang

doi:10.1016/j.bmcl.2011.12.065

Synthesis and evaluation of nitric oxide-releasing DDB derivatives as potential Pgp-mediated MDR reversal agents in MCF-7/Adr cells

Xiaobo Tang
, Xiaoke Gu
, Hua Ai
, Guangji Wang
, Hui Peng
, Yisheng Lai
, Yihua Zhang

China Pharmaceutical University
Institute of Basic Medical Sciences

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

20 Scopus citations

Abstract

Novel furoxan-based nitric oxide (NO)-releasing DDB derivatives (7a-j) were synthesized. Compounds 7i and 7j significantly reversed the resistance of MCF-7/Adr cells to doxorubicin in the combination treatment, and markedly increased the intracellular accumulation of doxorubicin probably via inhibiting Pgp-mediated intracellular drug efflux as well as down-regulating doxorubicin-induced Pgp expression. It was demonstrated that NO released by 7i and 7j played an important role in increasing intracellular doxorubicin accumulation and chemo-sensitizing MCF-7/Adr cells to doxorubicin, and the synergic effects of DDB and NO-donor moieties in 7i and 7j may contribute to reversing Pgp-mediated MDR in MCF-7/Adr cells to doxorubicin.

Original language	English
Pages (from-to)	801-805
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	2
DOIs	https://doi.org/10.1016/j.bmcl.2011.12.065
State	Published - 15 Jan 2012
Externally published	Yes

Keywords

DDB
MDR reversal agents
Multidrug resistance (MDR)
NO-releasing derivatives
Pgp inhibitor

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10.1016/j.bmcl.2011.12.065

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abstract = "Novel furoxan-based nitric oxide (NO)-releasing DDB derivatives (7a-j) were synthesized. Compounds 7i and 7j significantly reversed the resistance of MCF-7/Adr cells to doxorubicin in the combination treatment, and markedly increased the intracellular accumulation of doxorubicin probably via inhibiting Pgp-mediated intracellular drug efflux as well as down-regulating doxorubicin-induced Pgp expression. It was demonstrated that NO released by 7i and 7j played an important role in increasing intracellular doxorubicin accumulation and chemo-sensitizing MCF-7/Adr cells to doxorubicin, and the synergic effects of DDB and NO-donor moieties in 7i and 7j may contribute to reversing Pgp-mediated MDR in MCF-7/Adr cells to doxorubicin.",

keywords = "DDB, MDR reversal agents, Multidrug resistance (MDR), NO-releasing derivatives, Pgp inhibitor",

author = "Xiaobo Tang and Xiaoke Gu and Hua Ai and Guangji Wang and Hui Peng and Yisheng Lai and Yihua Zhang",

year = "2012",

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doi = "10.1016/j.bmcl.2011.12.065",

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T1 - Synthesis and evaluation of nitric oxide-releasing DDB derivatives as potential Pgp-mediated MDR reversal agents in MCF-7/Adr cells

AU - Tang, Xiaobo

AU - Gu, Xiaoke

AU - Ai, Hua

AU - Wang, Guangji

AU - Peng, Hui

AU - Lai, Yisheng

AU - Zhang, Yihua

PY - 2012/1/15

Y1 - 2012/1/15

N2 - Novel furoxan-based nitric oxide (NO)-releasing DDB derivatives (7a-j) were synthesized. Compounds 7i and 7j significantly reversed the resistance of MCF-7/Adr cells to doxorubicin in the combination treatment, and markedly increased the intracellular accumulation of doxorubicin probably via inhibiting Pgp-mediated intracellular drug efflux as well as down-regulating doxorubicin-induced Pgp expression. It was demonstrated that NO released by 7i and 7j played an important role in increasing intracellular doxorubicin accumulation and chemo-sensitizing MCF-7/Adr cells to doxorubicin, and the synergic effects of DDB and NO-donor moieties in 7i and 7j may contribute to reversing Pgp-mediated MDR in MCF-7/Adr cells to doxorubicin.

AB - Novel furoxan-based nitric oxide (NO)-releasing DDB derivatives (7a-j) were synthesized. Compounds 7i and 7j significantly reversed the resistance of MCF-7/Adr cells to doxorubicin in the combination treatment, and markedly increased the intracellular accumulation of doxorubicin probably via inhibiting Pgp-mediated intracellular drug efflux as well as down-regulating doxorubicin-induced Pgp expression. It was demonstrated that NO released by 7i and 7j played an important role in increasing intracellular doxorubicin accumulation and chemo-sensitizing MCF-7/Adr cells to doxorubicin, and the synergic effects of DDB and NO-donor moieties in 7i and 7j may contribute to reversing Pgp-mediated MDR in MCF-7/Adr cells to doxorubicin.

KW - DDB

KW - MDR reversal agents

KW - Multidrug resistance (MDR)

KW - NO-releasing derivatives

KW - Pgp inhibitor

UR - https://www.scopus.com/pages/publications/84855706085

U2 - 10.1016/j.bmcl.2011.12.065

DO - 10.1016/j.bmcl.2011.12.065

M3 - 文章

C2 - 22209486

AN - SCOPUS:84855706085

SN - 0960-894X

VL - 22

SP - 801

EP - 805

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 2

ER -

Synthesis and evaluation of nitric oxide-releasing DDB derivatives as potential Pgp-mediated MDR reversal agents in MCF-7/Adr cells

Abstract

Keywords

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