Direct Growth Control of Antibiotic-Resistant Bacteria Using Visible-Light-Responsive Novel Photoswitchable Antibiotics.
Chemistry
; 30(15): e202303685, 2024 Mar 12.
Article
em En
| MEDLINE
| ID: mdl-38217466
ABSTRACT
In addition to the discovery of new (modified) potent antibiotics to combat antibiotic resistance, there is a critical need to develop novel strategies that would restrict their off-target effects and unnecessary exposure to bacteria in our body and environment. We report a set of new photoswitchable arylazopyrazole-modified norfloxacin antibiotics that present a high degree of bidirectional photoisomerization, impressive fatigue resistance and reasonably high cis half-lives. The irradiated isomers of most compounds were found to exhibit nearly equal or higher antibacterial activity than norfloxacin against Gram-positive bacteria. Notably, against norfloxacin-resistant S.â
aureus bacteria, the visible-light-responsive p-SMe-substituted derivative showed remarkably high antimicrobial potency (MIC of 0.25â
µg/mL) in the irradiated state, while the potency was reduced by 24-fold in case of its non-irradiated state. The activity was estimated to be retained for more than 7â
hours. This is the first report to demonstrate direct photochemical control of the growth of antibiotic-resistant bacteria and to show the highest activity difference between irradiated and non-irradiated states of a photoswitchable antibiotic. Additionally, both isomers were found to be non-harmful to human cells. Molecular modellings were performed to identify the underlying reason behind the high-affinity binding of the irradiated isomer to topoisomerase IV enzyme.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Staphylococcus aureus Resistente à Meticilina
/
Anti-Infecciosos
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article