期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 30, 期 16, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2020.127302
关键词
Mitochondrial complex III; Inhibitor; Diaryl ether; Amide; Biological evaluation; Computational simulation
资金
- National Natural Science Foundation of China [21502062]
- Scientific Research Program Guiding Project of Hubei Provincial Department of Education [B2019135]
- Teachers' Scientific Research Ability Cultivation Fund, Hubei University of Arts and Science (Natural Science) [2018kypy001]
- Open Foundation of Discipline of Hubei University of Arts and Science [XK2019038, XK2019039]
Mitochondrial complex III is one of the most promising targets for a number of pharmaceuticals and fungicides. Due to the wide-spread use of complex III-inhibiting fungicides, a considerable increase of resistance has occurred worldwide. Therefore, inhibitors with novel scaffolds and potent activity against complex III are still in great demand. In this article, a new series of amide compounds bearing the diaryl ether scaffold were designed and prepared, followed by the biological evaluation. Gratifyingly, several compounds demonstrated potent activity against succinate-cytochrome c reductase (SCR, a mixture of mitochondrial complex II and complex III), with compound 3w possessing the best inhibitory activity (IC50 = 0.91 +/- 0.09 mu mol/L). Additional studies verified that 3w was a new inhibitor of complex III. Moreover, computational simulations elucidated that 3w should bind to the Q(o) site of complex III. We believe this work will be valuable for the preparation and discovery of more complex III inhibitors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据