Evaluation of multi-target iridium()-based metallodrugs in combating antimicrobial resistance and infections caused by
The rapid emergence and spread of multidrug-resistant bacteria pose a serious challenge to human life and health, necessitating the development of novel antibacterial agents. Herein, to address this challenge, three iridium-based antibacterial agents were prepared and their antimicrobial activity we...
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Veröffentlicht in: | RSC advances 2024-05, Vol.14 (23), p.16194-1626 |
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Zusammenfassung: | The rapid emergence and spread of multidrug-resistant bacteria pose a serious challenge to human life and health, necessitating the development of novel antibacterial agents. Herein, to address this challenge, three iridium-based antibacterial agents were prepared and their antimicrobial activity were explored. Importantly, the three complexes all showed robust potency against
S. aureus
with MIC values in the range of 1.9-7.9 μg mL
−1
. Notably, the most active complex
Ir3
also exhibited relative stability in mammalian fluids and a significant antibacterial effect on clinically isolated drug-resistant bacteria. Mechanism studies further demonstrated that the complex
Ir3
can kill
S. aureus
by disrupting the integrity of the bacterial membrane and inducing ROS production. This multi-target advantage allows
Ir3
to not only effectively combat bacterial resistance but also efficiently clear the bacterial biofilm. In addition, when used together, complex
Ir3
could enhance the antibacterial potency of some clinical antibiotics against
S. aureus
. Moreover, both
G. mellonella
wax worms and mouse infection model demonstrated that
Ir3
has low toxicity and robust anti-infective efficacy
in vivo
. Overall, complex
Ir3
can serve as a new antibacterial agent for combating Gram-positive bacterial infections.
Ir3
can kill
S. aureus
by disrupting the integrity of the bacterial membrane and inducing ROS production. Both
G. mellonella
wax worms and mouse infection model demonstrated that
Ir3
has low toxicity and robust anti-infective efficacy
in vivo
. |
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ISSN: | 2046-2069 |
DOI: | 10.1039/d4ra02152e |