Conjugated carbon monoxide-releasing molecules have broad-spectrum antimicrobial activity

Future Med Chem. 2023 Jun;15(12):1037-1048. doi: 10.4155/fmc-2023-0103. Epub 2023 Jul 17.

Abstract

Aim: To test the antimicrobial effect of carbon monoxide-releasing molecules (CORMs) conjugated with azoles on different microorganisms. Methods & results: We used broth microdilution, checkerboard and cytotoxicity assays, as well as imaging, fluorescence and bioluminescence experiments to study [Re(CO)3(2,2'-bipyridyl)(Ctz)]+ (also known as ReBpyCtz). ReBpyCtz exhibits a low minimum inhibitory concentration value, increases the intracellular formation of reactive oxygen species and causes significant alterations on Staphylococcus aureus's membrane. ReBpyCtz is active against fungi, having a more prolonged fungicidal effect on Candida glabrata than clotrimazole and is selectively active on blood-stage malaria parasites, at a concentration that is not toxic to kidney epithelial cells. Conclusion: Conjugated CORMs have the potential to be active against different types of pathogens, thus constituting a promising class of broad-spectrum antimicrobials.

Keywords: Candida spp.; Plasmodium spp.; Staphylococcus aureus; antimicrobials; carbon monoxide-releasing molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents* / pharmacology
  • Carbon Monoxide* / pharmacology
  • Epithelial Cells
  • Fungi
  • Microbial Sensitivity Tests

Substances

  • Carbon Monoxide
  • Anti-Infective Agents