Identification of a novel small molecule targeting UQCRB of mitochondrial complex III and its anti-angiogenic activity
Identification of a novel small molecule targeting UQCRB of mitochondrial complex III and its anti-angiogenic activity
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DOI：
10.1016/j.bmcl.2010.12.002
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发表时间：
2011-02-01
影响因子：
2.7
通讯作者：
Kwon, Ho Jeong
中科院分区：
文献类型：
--
作者：
Jung, Hye Jin;Kim, Ki Hyun;Kwon, Ho Jeong
Our recent study has shown that ubiquinol-cytochrome c reductase binding protein (UQCRB), the 13.4-kDa subunit of mitochondrial complex III, plays a crucial role in hypoxia-induced angiogenesis via mitochondrial reactive oxygen species (ROS)-mediated signaling. Here we report a new synthetic small molecule targeting the mitochondrial oxygen sensor UQCRB that was identified by pharmacophore-based virtual screening and in vitro and in vivo competition binding analyses. 6-((1-Hydroxynaphthalen-4-ylamino) dioxysulfone)-2H-naphtho[1,8-bc]thiophen-2-one (HDNT) binds to the hydrophobic pocket of UQCRB and potently inhibits in vitro angiogenesis of human umbilical vein endothelial cells without cytotoxicity. Furthermore, the binding of HDNT to UQCRB suppressed mitochondrial ROS-mediated hypoxic signal transduction. These results demonstrated that HDNT is a novel synthetic small molecule targeting UQCRB and exhibits anti-angiogenic activity by modulating the oxygen-sensing function of UQCRB. (C) 2010 Elsevier Ltd. All rights reserved.
