Characterization of a versatile organometallic pro-drug (CORM) for experimental CO based therapeutics

用于实验性 CO 疗法的多功能有机金属前药 (CORM) 的表征

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作者:João D Seixas, Abhik Mukhopadhyay, Teresa Santos-Silva, Leo E Otterbein, David J Gallo, Sandra S Rodrigues, Bruno H Guerreiro, Ana M L Gonçalves, Nuno Penacho, Ana R Marques, Ana C Coelho, Patrícia M Reis, Maria J Romão, Carlos C Romão

Abstract

The complex fac-[Mo(CO)(3)(histidinate)]Na has been reported to be an effective CO-Releasing Molecule in vivo, eliciting therapeutic effects in several animal models of disease. The CO releasing profile of this complex in different settings both in vitro and in vivo reveals that the compound can readily liberate all of its three CO equivalents under biological conditions. The compound has low toxicity and cytotoxicity and is not hemolytic. CO release is accompanied by a decrease in arterial blood pressure following administration in vivo. We studied its behavior in solution and upon the interaction with proteins. Reactive oxygen species (ROS) generation upon exposure to air and polyoxomolybdate formation in soaks with lysozyme crystals were observed as processes ensuing from the decomposition of the complex and the release of CO.

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