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<a href="http://doi.org/10.1021/acs.jmedchem.1c00656" target="_blank" rel="noreferrer noopener">http://doi.org/10.1021/acs.jmedchem.1c00656</a>
ISSN
1520-4804 0022-2623
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<a href="http://neomed.idm.oclc.org/login?url=http://doi.org/10.1021/acs.jmedchem.1c00656" target="_blank" rel="noreferrer noopener">NEOMED Full-text Holding (if available) - Proxy DOI: 10.1021/acs.jmedchem.1c00656</a>
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Update Year & Number
June 2021 List
NEOMED College
NEOMED College of Medicine
NEOMED Department
Department of Integrative Medical Sciences
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Title
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Lipophilic Ga Complex with Broad-Spectrum Antimicrobial Activity and the Ability to Overcome Gallium Resistance in both Pseudomonas aeruginosa and Staphylococcus aureus.
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Journal Of Medicinal Chemistry
Date
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2021
2021-06-17
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Wang Z; Li J; Benin BM;Yu B; Bunge Scott D; Abeydeera N; Huang SD; Kim M-H
Description
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Antibiotic resistance (AR) necessitates the discovery of new antimicrobials with alternative mechanisms of action to those employed by conventional antibiotics. One such strategy utilizes Ga(3+) to target iron metabolism, a critical process for survival. Still, Ga-based therapies are generally ineffective against Gram-positive bacteria and promote Ga resistance. In response to these drawbacks, we report a lipophilic Ga complex, [Ga(2)L(3)(bpy)(2)] (L = 2,2'-bis(3-hydroxy-1,4-naphthoquinone; bpy = 2,2'-bipyridine)), effective against drug-resistant Pseudomonas aeruginosa (DRPA; minimum inhibitory concentration, MIC = 10 μM = 14.8 μg/mL) and methicillin-resistant Staphylococcus aureus (MRSA, MIC = 100 μM = 148 μg/mL) without iron-limited conditions. Importantly, [Ga(2)L(3)(bpy)(2)] shows noticeably delayed and decreased resistance in both MRSA and DRPA, with only 8× MIC in DRPA and none in MRSA after 30 passages. This is likely due to the dual mode of action afforded by Ga (disruption of iron metabolism) and the ligand (reactive oxygen species production). Overall, [Ga(2)L(3)(bpy)(2)] demonstrates the utility of lipophilic metal complexes with multiple modes of action in combatting AR in Gram-positive and Gram-negative bacteria.
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<a href="http://doi.org/10.1021/acs.jmedchem.1c00656" target="_blank" rel="noreferrer noopener">10.1021/acs.jmedchem.1c00656</a>
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journalArticle
2021
Abeydeera N
Benin BM
Bunge Scott D
Department of Integrative Medical Sciences
Huang SD
Journal of medicinal chemistry
journalArticle
June 2021 List
Kim M-H
Li J
NEOMED College of Medicine
Wang Z
Yu B