Metalloenzyme mimicry and modulation strategies to conquer antimicrobial resistance: Metal-ligand coordination perspectives
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Date
2021-11-24
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Elsevier
Abstract
The incessant resistivity of pathogenic microbes to antibiotics continuously constitutes a major threat to
human wellness, thus, searching for effective therapeutic approaches remains essential. Metalloenzymes
such as erythromycin esterases, b-lactamases, N-acetyltransferases, staphylopine dehydrogenases significantly
confer antibiotic resistance and cell defence in superbugs including Escherichia coli, Pseudomonas
aeruginosa, Klebsiella pneumonia, Helicobacter pylori and Staphylococcus aureus. These occur through various
pathomechanisms including modulations of intracellular targets, hydrolytic cleavage and cellular
metabolism of antibiotics, redox catalysis, and oftentimes via the attraction/donation of electrons during
labile coordination to substrates. Several inhibitors of these therapeutic pathways have been reported
including metal chelators and chelates. However, the overview of these innovative anti-resistance strategies
remains sparse. We hereby present a comprehensive review of the coordination chemistry of metalloenzymes
in the resistance development and modulatory potentials of metal-chelating and metal
complex inhibitors for catalytic deactivation. These include the removal/replacement of biotic metal ions
and/or chelating agents to induce loss of resistivity and specificity, and suppression of catalytic activities
as potential therapeutic strategies. Selectively, imipenem, meropenem, hesperidin, aspergillomarasmine
A, picolinic, rosmarinic and salvianolic acids represent potent metal-chelating inhibitors of the
metallo-b-lactamases, ligands B67-B78 as promising candidates against ureases, while B79-B83 effectively
suppressed catalysis of polyphenol oxidases. Some metal chelates also demonstrated potentials
to mitigate the defence/resistivity of the metalloenzymes hypothetically through the acquisition of abiotic
metals ions, accumulation of antimicrobial ligands and blockage of active metalloenzyme sites. This
review represents a model for innovative therapeutic strategies to overcome antimicrobial resistance
through metalloenzyme mimicry and modulation for further studies
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Citation
Ayipo Y. O., Osunniran W. A., Babamale H. F., Ayinde M. O. Mordi M. N., Metalloenzyme mimicry and modulation strategies to conquer antimicrobial resistance: Metal-ligand coordination perspectives, Coordination Chemistry Reviews, 2022, 453(2) 214317 https://doi.org/10.1016/j.ccr.2021.214317