Diverse Nrf2 Activators Coordinated to Cobalt Carbonyls Induce Heme Oxygenase-1 and Release Carbon Monoxide in Vitro and in Vivo
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- 作者：Aniket Nikam ; Anthony Ollivier ; Michael Rivard ; Jayne Louise Wilson ; Kevin Mebarki ; Thierry Martens ; Jean-Luc Dubois-Randé ; Roberto Motterlini ; Roberta Foresti
- 刊名：Journal of Medicinal Chemistry
- 出版年：2016
- 出版时间：January 28, 2016
- 年：2016
- 卷：59
- 期：2
- 页码：756-762
- 全文大小：398K
- ISSN：1520-4804
文摘
The Nrf2/heme oxygenase-1 (HO-1) axis affords significant protection against oxidative stress and cellular damage. We synthesized a series of cobalt-based hybrid molecules (HYCOs) that combine an Nrf2 inducer with a releaser of carbon monoxide (CO), an anti-inflammatory product of HO-1. Two HYCOs markedly increased Nrf2/HO-1 expression, liberated CO and exerted anti-inflammatory activity in vitro. HYCOs also up-regulated tissue HO-1 and delivered CO in blood after administration in vivo, supporting their potential use against inflammatory conditions.