European Journal of Medicinal Chemistry, volume 257, pages 115462
Discovery of 2,5-disubstituted furan derivatives featuring a benzamide motif for overcoming P-glycoprotein mediated multidrug resistance in MCF-7/ADR cell
Zhikun Yang
1
,
Yue Cai
1
,
Ming Jun Shen
1
,
Qihao Wu
2
,
Mengdi Zhu
3
,
Xiaoji Cao
3
,
Bin Wei
1
,
Jin Miao Tian
1
,
Xiaoze Bao
1
,
Xinyi Ye
1
,
Jianwei Chen
1
,
Sijia Wang
1
,
Yanlei Yu
1
,
Huawei Zhang
1
,
Xuanrong Sun
1
,
Zi-Ning Cui
4
,
Yasheng Li
5
,
Publication type: Journal Article
Publication date: 2023-09-01
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 6.7
ISSN: 02235234, 17683254
Organic Chemistry
Drug Discovery
General Medicine
Pharmacology
Abstract
P-glycoprotein (P-gp) is one of the drug efflux transporters that triggers multidrug resistance (MDR) in cells. Herein, by utilizing the strategies of active skeleton splicing and structural optimization on the lead compound 5 m, a total of 50 novel 2,5-disubstituted furan derivatives were designed, synthesized, and screened for P-gp inhibitory activity. The structure-activity relationship analysis enabled the identification of an important pharmacophore N-phenylbenzamide, which resulted in the discovery of a promising drug lead compound Ⅲ-8. Ⅲ-8 possesses broad-spectrum reversal activity and low toxicity in MCF-7/ADR cells. Western blot and Rh123 accumulation assay demonstrated that Ⅲ-8 displayed the reversal activity by inhibiting P-gp efflux. Molecular docking analysis indicated a potent affinity of Ⅲ-8 to P-gp by forming H-bond interactions with residues Asn 721 and Met 986. Ⅲ-8 was determined to be a highly effective and safe P-gp inhibitor in an MCF-7/ADR xenograft mouse model.
Top-30
Citations by journals
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European Journal of Medicinal Chemistry
2 publications, 50%
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RSC Medicinal Chemistry
1 publication, 25%
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Russian Chemical Reviews
1 publication, 25%
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1
2
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Citations by publishers
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1
2
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Elsevier
2 publications, 50%
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Royal Society of Chemistry (RSC)
1 publication, 25%
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Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii
1 publication, 25%
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1
2
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- We do not take into account publications without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Yang Z. et al. Discovery of 2,5-disubstituted furan derivatives featuring a benzamide motif for overcoming P-glycoprotein mediated multidrug resistance in MCF-7/ADR cell // European Journal of Medicinal Chemistry. 2023. Vol. 257. p. 115462.
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Yang Z., Cai Y., Shen M. J., Wu Q., Zhu M., Cao X., Wei B., Tian J. M., Bao X., Ye X., Chen J., Wang S., Yu Y., Zhang H., Sun X., Cui Z., Li Y., Wang H. Discovery of 2,5-disubstituted furan derivatives featuring a benzamide motif for overcoming P-glycoprotein mediated multidrug resistance in MCF-7/ADR cell // European Journal of Medicinal Chemistry. 2023. Vol. 257. p. 115462.
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TY - JOUR
DO - 10.1016/j.ejmech.2023.115462
UR - https://doi.org/10.1016/j.ejmech.2023.115462
TI - Discovery of 2,5-disubstituted furan derivatives featuring a benzamide motif for overcoming P-glycoprotein mediated multidrug resistance in MCF-7/ADR cell
T2 - European Journal of Medicinal Chemistry
AU - Yang, Zhikun
AU - Cai, Yue
AU - Shen, Ming Jun
AU - Wu, Qihao
AU - Zhu, Mengdi
AU - Cao, Xiaoji
AU - Wei, Bin
AU - Tian, Jin Miao
AU - Bao, Xiaoze
AU - Ye, Xinyi
AU - Chen, Jianwei
AU - Wang, Sijia
AU - Yu, Yanlei
AU - Zhang, Huawei
AU - Sun, Xuanrong
AU - Cui, Zi-Ning
AU - Li, Yasheng
AU - Wang, Hong
PY - 2023
DA - 2023/09/01 00:00:00
PB - Elsevier
SP - 115462
VL - 257
SN - 0223-5234
SN - 1768-3254
ER -
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@article{2023_Yang,
author = {Zhikun Yang and Yue Cai and Ming Jun Shen and Qihao Wu and Mengdi Zhu and Xiaoji Cao and Bin Wei and Jin Miao Tian and Xiaoze Bao and Xinyi Ye and Jianwei Chen and Sijia Wang and Yanlei Yu and Huawei Zhang and Xuanrong Sun and Zi-Ning Cui and Yasheng Li and Hong Wang},
title = {Discovery of 2,5-disubstituted furan derivatives featuring a benzamide motif for overcoming P-glycoprotein mediated multidrug resistance in MCF-7/ADR cell},
journal = {European Journal of Medicinal Chemistry},
year = {2023},
volume = {257},
publisher = {Elsevier},
month = {sep},
url = {https://doi.org/10.1016/j.ejmech.2023.115462},
pages = {115462},
doi = {10.1016/j.ejmech.2023.115462}
}
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