Potent Inhibition of Nitric Oxide-Releasing Bifendate Derivatives against Drug-Resistant K562/A02 Cells in Vitro and in Vivo
Xiaoke Gu
1, 2
,
Zhangjian Huang
1
,
Zhiguang Ren
3
,
Xiaobo Tang
1
,
Rongfang Xue
1
,
Xiaojun Luo
1
,
Sixun Peng
1
,
Hui Peng
3
,
Bin Lu
4
,
Jide Tian
5
,
2
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, People’s Republic of China
|
3
Department of Environment and Pharmacy, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, People’s Republic of China
|
Publication type: Journal Article
Publication date: 2017-01-18
scimago Q1
wos Q1
SJR: 1.801
CiteScore: 11.5
Impact factor: 6.8
ISSN: 00222623, 15204804
PubMed ID:
28068095
Drug Discovery
Molecular Medicine
Abstract
Multidrug resistance is a major obstacle to successful chemotherapy for leukemia. In this study, a series of nitric oxide (NO)-releasing bifendate derivatives (7a-n) were synthesized. Biological evaluation indicated that the most active compound (7a) produced relatively high levels of NO and significantly inhibited the proliferation of drug-resistant K562/A02 cells in vitro and in vivo. In addition, 7a induced the mitochondrial tyrosine nitration and the intracellular accumulation of rhodamine 123 by inhibiting P-gp activity in K562/A02 cells. Furthermore, 7a remarkably down-regulated AKT, NF-κB, and ERK activation and HIF-1α expression in K562/A02 cells, which are associated with the tumor cell proliferation and drug resistance. Notably, the antitumor effects were dramatically attenuated by an NO scavenger or elimination of the NO-releasing capability of 7a, indicating that NO produced by 7a contributed to, at least partly, its cytotoxicity against drug-resistant K562/A02 cells. Overall, 7a may be a potential agent against drug-resistant myelogenous leukemia.
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Total citations:
35
Citations from 2024:
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(11%)
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GOST
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Gu X. et al. Potent Inhibition of Nitric Oxide-Releasing Bifendate Derivatives against Drug-Resistant K562/A02 Cells in Vitro and in Vivo // Journal of Medicinal Chemistry. 2017. Vol. 60. No. 3. pp. 928-940.
GOST all authors (up to 50)
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Gu X., Huang Z., Ren Z., Tang X., Xue R., Luo X., Peng S., Peng H., Lu B., Tian J., Zhang Y. Potent Inhibition of Nitric Oxide-Releasing Bifendate Derivatives against Drug-Resistant K562/A02 Cells in Vitro and in Vivo // Journal of Medicinal Chemistry. 2017. Vol. 60. No. 3. pp. 928-940.
Cite this
RIS
Copy
TY - JOUR
DO - 10.1021/acs.jmedchem.6b01075
UR - https://doi.org/10.1021/acs.jmedchem.6b01075
TI - Potent Inhibition of Nitric Oxide-Releasing Bifendate Derivatives against Drug-Resistant K562/A02 Cells in Vitro and in Vivo
T2 - Journal of Medicinal Chemistry
AU - Gu, Xiaoke
AU - Huang, Zhangjian
AU - Ren, Zhiguang
AU - Tang, Xiaobo
AU - Xue, Rongfang
AU - Luo, Xiaojun
AU - Peng, Sixun
AU - Peng, Hui
AU - Lu, Bin
AU - Tian, Jide
AU - Zhang, Yihua
PY - 2017
DA - 2017/01/18
PB - American Chemical Society (ACS)
SP - 928-940
IS - 3
VL - 60
PMID - 28068095
SN - 0022-2623
SN - 1520-4804
ER -
Cite this
BibTex (up to 50 authors)
Copy
@article{2017_Gu,
author = {Xiaoke Gu and Zhangjian Huang and Zhiguang Ren and Xiaobo Tang and Rongfang Xue and Xiaojun Luo and Sixun Peng and Hui Peng and Bin Lu and Jide Tian and Yihua Zhang},
title = {Potent Inhibition of Nitric Oxide-Releasing Bifendate Derivatives against Drug-Resistant K562/A02 Cells in Vitro and in Vivo},
journal = {Journal of Medicinal Chemistry},
year = {2017},
volume = {60},
publisher = {American Chemical Society (ACS)},
month = {jan},
url = {https://doi.org/10.1021/acs.jmedchem.6b01075},
number = {3},
pages = {928--940},
doi = {10.1021/acs.jmedchem.6b01075}
}
Cite this
MLA
Copy
Gu, Xiaoke, et al. “Potent Inhibition of Nitric Oxide-Releasing Bifendate Derivatives against Drug-Resistant K562/A02 Cells in Vitro and in Vivo.” Journal of Medicinal Chemistry, vol. 60, no. 3, Jan. 2017, pp. 928-940. https://doi.org/10.1021/acs.jmedchem.6b01075.
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