Development of photoactivable phenanthroline-based manganese(I) CO-Releasing molecules (PhotoCORMs) active against ESKAPE bacteria and bacterial biofilms

TY - JOUR

T1 - Development of photoactivable phenanthroline-based manganese(I) CO-Releasing molecules (PhotoCORMs) active against ESKAPE bacteria and bacterial biofilms

AU - Toscani, Anita

AU - Hind, Charlotte

AU - Clifford, Melanie

AU - Kim, Seong Heun

AU - Gucic, Antonia

AU - Woolley, Charlotte

AU - Saeed, Naima

AU - Rahman, Khondaker Miraz

AU - Sutton, J. Mark

AU - Castagnolo, Daniele

N1 - Funding Information: University of London is gratefully acknowledged for the CW Maplethorpe Fellowship to AT. NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research, NC/T001240/1) is acknowledged for research funding. Publisher Copyright: © 2021 Elsevier Masson SAS Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/3/5

Y1 - 2021/3/5

N2 - 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.

AB - 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.

KW - antibacterial

KW - biofilm

KW - Carbon monoxide

KW - CORM

KW - photoactivation

UR - http://www.scopus.com/inward/record.url?scp=85099851561&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2021.113172

DO - 10.1016/j.ejmech.2021.113172

M3 - Article

AN - SCOPUS:85099851561

SN - 0223-5234

VL - 213

JO - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

JF - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

M1 - 113172

ER -