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Biological Activity of Designed Photolabile Metal Nitrosyls:? Light-Dependent Activation of Soluble Guanylate Cyclase and Vasorelaxant Properties in Rat Aorta

Authors :
Madhani, Melanie
K. Patra, Apurba
W. Miller, Thomas
A. Eroy-Reveles, Aura
J. Hobbs, Adrian
M. Fukuto, Jon
K. Mascharak, Pradip
Source :
Journal of Medicinal Chemistry; December 2006, Vol. 49 Issue: 25 p7325-7330, 6p
Publication Year :
2006

Abstract

The biological and pharmacological utility of nitric oxide (NO) has led to the development of many classes of NO-donor compounds as both research tools and therapeutic agents. Many donors currently in use rely on thermal decomposition or bioactivation for the release of NO. We have developed several photolabile metal-nitrosyl donors that release NO when exposed to either visible or UV light. Herein, we show that these donors are capable of activating the primary “NO receptor”, soluble guanylate cyclase (sGC), in a light-dependent fashion leading to increases in cGMP. Moreover, we demonstrate that these donors are capable of eliciting light-dependent increases of cGMP in smooth muscle cells and vasorelaxation of rat aortic smooth muscle tissue, all effects that are attributed to activation of sGC. The potential utility of these compounds as drugs and/or research tools is discussed.

Details

Language :
English
ISSN :
00222623 and 15204804
Volume :
49
Issue :
25
Database :
Supplemental Index
Journal :
Journal of Medicinal Chemistry
Publication Type :
Periodical
Accession number :
ejs10802561
Full Text :
https://doi.org/10.1021/jm0604629