Article ID Journal Published Year Pages File Type
1370938 Bioorganic & Medicinal Chemistry Letters 2011 5 Pages PDF
Abstract

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.

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Physical Sciences and Engineering Chemistry Organic Chemistry
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