Abstract

The endogenous catabolism of (toxic) heme released from injured or dead cells or from heme proteins recycling/metabolism is effected by the heme oxygenase (HO) enzymes, namely the inducible isoform HO-1. This enzymatic heme oxidation produces biliverdin, Fe2+ ions and carbon monoxide (CO). HO enzymatic activity correlates with an extensive immune and cytoprotective activity, which is also essentially replicated by administration of exogenous CO. In order to translate the strong biological and therapeutic potential of the HO/CO axis, CO-releasing molecules (CORM) that deliver CO specifically to the diseased tissues, thus circumventing the toxicity of high doses of inhaled CO, have been proposed. These prodrugs are transition metal carbonyl complexes and the therapeutic effects of early-stage CORMs are described in inflammatory, cardiovascular, and central nervous system diseases, as well as in cancer, transplantation, tissue regeneration, and bacterial killing. Based on abundant proofs of concept and a detailed analysis of the chemical biology of the early-stage CORMs, the strategies for the design of advanced, second-generation prodrugs and devices for targeted delivery of CO are presented and discussed, including photoactivated, bioactivated, and pharmacologically advanced drug-like CORMs. The most recent methodologies for detection and tracking of CO in biological contexts are also presented and discussed in this chapter.

Original languageEnglish
Title of host publicationMetal Carbonyl Prodrugs: CO Delivery and Beyond
PublisherWILEY-BLACKWELL
Number of pages38
ISBN (Electronic)9783527673438
ISBN (Print)9783527335275
DOIs
Publication statusPublished - 27 Apr 2015

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Keywords

  • Bioorganometallic chemistry
  • Carbon monoxide
  • CO-releasing molecules
  • CORMs
  • Cytoprotection
  • Gasotransmitters
  • Inflammation
  • Metal carbonyls
  • Metal-based drugs

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