1. Characterization of a versatile organometallic pro-drug (CORM) for experimental CO based therapeutics.
- Author
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Seixas JD, Mukhopadhyay A, Santos-Silva T, Otterbein LE, Gallo DJ, Rodrigues SS, Guerreiro BH, Gonçalves AM, Penacho N, Marques AR, Coelho AC, Reis PM, Romão MJ, and Romão CC
- Subjects
- Animals, Binding Sites, Cell Line, Cell Survival drug effects, Coordination Complexes chemical synthesis, Coordination Complexes toxicity, Crystallography, X-Ray, Hemodynamics, Hemoglobins chemistry, Hemoglobins metabolism, Hemolysis, Hep G2 Cells, Humans, Mice, Muramidase chemistry, Muramidase metabolism, Organometallic Compounds chemical synthesis, Organometallic Compounds toxicity, Prodrugs chemical synthesis, Prodrugs toxicity, Protein Structure, Tertiary, Serum Albumin chemistry, Serum Albumin metabolism, Carbon Monoxide metabolism, Coordination Complexes chemistry, Organometallic Compounds chemistry, Prodrugs chemistry
- 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.
- Published
- 2013
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