期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 64, 期 24, 页码 4830-4837出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.6b00325
关键词
succinate-ubiquinone oxidoreductase; complex II; pharmacophore-linked fragment virtual screening; molecular modeling; structure-based design
资金
- Special Fund for Agro-scientific Research in the Public Interest [201203022]
- National Natural Science Foundation of China [21332004, 21272092]
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 value 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 respect to the substrate cytochrome c and DCIP. Interestingly, compounds 8a, 9h, 9j, and 9k exhibited good in vivo preventive effects against Rhizoctonia solani. The results obtained from molecular modeling showed that the orientation of the R-2 group had a significant effect on binding with the protein.
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