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  • Development of photoactivab...
    Toscani, Anita; Hind, Charlotte; Clifford, Melanie; Kim, Seong-Heun; Gucic, Antonia; Woolley, Charlotte; Saeed, Naima; Rahman, Khondaker Miraz; Sutton, J. Mark; Castagnolo, Daniele

    European journal of medicinal chemistry, 03/2021, Letnik: 213
    Journal Article

    The synthesis and biological evaluation of a series of phenanthroline-based visible-light-activated manganese(I) carbon-monoxide-releasing molecules (PhotoCORMs) against ESKAPE bacteria and bacterial biofilms is reported. Four carbonyl compounds of general formula fac-Mn(N∧N)(CO)3(L) have been synthesized and characterized. Despite being thermally stable in the absence of light, these PhotoCORMs readily release CO upon blue (435–450 nm) LED light irradiation as confirmed by spectrophotometric CO releasing experiments (Mb Assay). The antibacterial activity of the four PhotoCORMs has been investigated against a panel of ESKAPE bacteria. The compounds 1–3 were found to be effective antibacterials at low concentrations against multidrug-resistant Klebsiella pneumoniae and Acinetobacter baumannii when photoactivated with blue-light. In addition, the PhotoCORMs 1–2 were found to inhibit the formation of Klebsiella pneumoniae and Acinetobacter baumannii bacterial biofilms at low concentrations (MIC = 4–8 μg/mL), turning out to be promising candidates to combat antimicrobial resistance. The antibacterial and biofilm inhibitory effect of the PhotoCORMs is plausibly due to the release of CO as well as the formation of phenanthroline photo-by-products as revealed by spectroscopy and microbiology experiments. Display omitted •Phenanthroline-based manganese(I) PhotoCORMs were synthesized and found to possess antibacterial activity.•PhotoCORMs release carbon monoxide (CO) when irradiated with visible light (blue or green).•PhotoCORMs show antibacterial activity against Gram negative bacteria when irradiated with blue LED light.•PhotoCORMs inhibit the formation of Klebsiella pneumoniae and Acinetobacter baumannii biofilms at low concentrations.•The release of CO and the formation of photo-by-products are responsible for the antibacterial and anti-biofilm activity.