title: Characterization of a versatile organometallic pro-drug (CORM) for experimental CO based therapeutics.
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.
authors.affiliation: Alfama Lda, Taguspark, núcleo central 267, 2740-122 Porto Salvo, Portugal.
authors.forename: João D
authors.initials: JD
authors.lastname: Seixas
authors.forename: Abhik
authors.initials: A
authors.lastname: Mukhopadhyay
authors.forename: Teresa
authors.initials: T
authors.lastname: Santos-Silva
authors.forename: Leo E
authors.initials: LE
authors.lastname: Otterbein
authors.forename: David J
authors.initials: DJ
authors.lastname: Gallo
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Rodrigues
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Guerreiro
authors.forename: Ana M L
authors.initials: AM
authors.lastname: Gonçalves
authors.forename: Nuno
authors.initials: N
authors.lastname: Penacho
authors.forename: Ana R
authors.initials: AR
authors.lastname: Marques
authors.forename: Ana C
authors.initials: AC
authors.lastname: Coelho
authors.forename: Patrícia M
authors.initials: PM
authors.lastname: Reis
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Romão
authors.forename: Carlos C
authors.initials: CC
authors.lastname: Romão
mesh_terms: D000818:Animals; D001665:Binding Sites; D002248:Carbon Monoxide / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D018360:Crystallography, X-Ray; D006439:Hemodynamics; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D006461:Hemolysis; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism
chemical_list: C583832:ALF168; D056831:Coordination Complexes; D006454:Hemoglobins; D009942:Organometallic Compounds; D011355:Prodrugs; D012709:Serum Albumin; D002248:Carbon Monoxide; D009113:Muramidase