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Discovery of Potent Succinate-Ubiquinone Oxidoreductase Inhibitors via Pharmacophore-linked Fragment Virtual Screening Approach

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成果类型:
期刊论文
作者:
Xiong, Li;Zhu, Xiao-Lei*;Gao, Hua-Wei;Fu, Yu(杨光富);Hu, Sheng-Quan;...
通讯作者:
Zhu, Xiao-Lei;Yang, Guang-Fu
作者机构:
[Fu, Yu; Hu, Sheng-Quan; Zhu, Xiao-Lei; Xiong, Li; Yang, Wen-Chao; Gao, Hua-Wei; Jiang, Li-Na] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
[Fu, Yu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
[Zhu, XL; Yang, GF] Ctr China Normal Univ, Luoyu Rd 152, Wuhan 43007, Peoples R China.
通讯机构:
[Zhu, XL; Yang, GF] C
Ctr China Normal Univ, Luoyu Rd 152, Wuhan 43007, Peoples R China.
语种:
英文
关键词:
succinate-ubiquinone oxidoreductase;complex II;pharmacophore-linked fragment virtual screening;molecular modeling;structure-based design
期刊:
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
ISSN:
0021-8561
年:
2016
卷:
64
期:
24
页码:
4830-4837
基金类别:
Special Fund for Agro-scientific Research in the Public Interest [201203022]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21332004, 21272092]
机构署名:
本校为第一且通讯机构
院系归属:
化学学院
摘要:
Succinate-ubiquinone oxidoreductase (SQR) is an attractive target for fungicide discovery. Herein, we report the discovery of novel SQR inhibitors using a pharmacophore-linked fragment virtual screening approach, a new drug design method developed in our laboratory. Among newly designed compounds, compound 9s was identified as the most potent inhibitor with a Kivalue of 34 nM against porcine SQR, displaying approximately 10-fold higher potency than that of the commercial control penthiopyrad. Further inhibitory kinetics studies revealed that compound 9s is a noncompetitive inhibitor with respe...

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