[SCAN Highlight] Examining the antimicrobial activity and toxicity to animal cells of different types of CO-releasing molecules

SCAN Paper Highlight

Title: Examining the antimicrobial activity and toxicity to animal cells of different types of CO-releasing molecules

Speaker: Lígia Nobre

Affiliation: Lígia M. Saraiva Lab

Paper

Examining the antimicrobial activity and toxicity to animal cells of different types of CO-releasing molecules

Lígia S. Nobre, Hélia Jeremias, Carlos C. Romão and Lígia M. Saraiva

Dalton Trans. 2016 Jan 19;45(4):1455-66

Transition metal carbonyl complexes used as CO-releasing molecules (CORMs) for biological and therapeutic applications exhibit interesting antimicrobial activity. However, understanding the chemical traits and mechanisms of action that rule this activity is required to establish a rationale for the development of CORMs into useful antibiotics. In this work the bactericidal activity, the toxicity to eukaryotic cells, and the ability of CORMs to deliver CO to bacterial and eukaryotic cells were analysed for a set of seven CORMs that differ in the transition metal, ancillary ligands and the CO release profile.
Most of the CORMs studied exhibited antimicrobial activity and induced the formation of reactive oxygen species (ROS) inside Escherichia coli. Moreover, the amount of intracellularly ROS was, in general, proportional to the CORM strength as bactericide. In contrast, studies in model animal cells showed that CORMs were in general not toxic to eukaryotic cells, namely murine macrophages, kidney epithelial cells, and liver cells and for any given CORM, the level of intracellular ROS generated was negligible when compared with that measured inside bacteria.
Importantly, the most efficient bactericides, CORM-2 and CORM-3, delivered CO to the intracellular space of both E. coli and to eukaryotic cells, yet toxicity was only elicited in the case of E. coli. Altogether, our results suggest that CORMs have a relevant therapeutic potential as antimicrobial drugs since (i) they can show opposite toxicity profiles towards bacteria and eukaryotic cells; (ii) their activity can be modulated through manipulation of the ancillary ligands and (iii) their toxicity to eukaryotic cells can be made acceptably low. With this new approach, this work contributes to the understanding of the roots of the bactericidal action of CORMs and helps in establishing strategies for their development into a new class of antibiotics.