Carmofur Exhibits Antimicrobial Activity Against Streptococcus pneumoniae DOI Creative Commons

Wenting Lyu,

Yuqing Zhang, Zhen Zhang

и другие.

Antibiotics, Год журнала: 2025, Номер 14(3), С. 231 - 231

Опубликована: Фев. 25, 2025

Background/Objectives: Streptococcus pneumoniae (S. pneumoniae) is a major pathogen causing severe infectious diseases, with an escalating issue of antimicrobial resistance that threatens the efficacy existing antibiotics. Given challenges in developing traditional antibiotics, drug repurposing strategies offer novel approach to address crisis. This study aims evaluate antibacterial and anti-biofilm activities approved non-antibiotic anticancer carmofur against multidrug-resistant S. pneumoniae, investigate mechanism action, assess therapeutic potential vivo. Methods/Results: Antimicrobial tests revealed exhibited strong activity strains, minimum inhibitory concentrations (MICs) ranging from 0.25 1 µg/mL. In biofilm detection experiments, not only inhibited formation biofilms, but also effectively removed biofilms under high concentration conditions. Mechanistic studies showed disrupted bacterial membrane permeability decreased intracellular ATP levels. Molecular docking dynamics simulation assays indicated could stably bind thymidylate synthase through hydrogen bonding hydrophobic interactions, thereby exerting effects. Meanwhile, was able repress expression thyA gene at mRNA level. mouse infection model, treatment group reduction approximately two log levels load lung tissue blood, significant decrease inflammatory cytokines TNF-α IL-6, improvement survival rate 60%. Conclusions: summary, demonstrated good anti-infective effects vivo, suggesting its clinical application as agent drug-resistant bacteria.

Язык: Английский

Carmofur Exhibits Antimicrobial Activity Against Streptococcus pneumoniae DOI Creative Commons

Wenting Lyu,

Yuqing Zhang, Zhen Zhang

и другие.

Antibiotics, Год журнала: 2025, Номер 14(3), С. 231 - 231

Опубликована: Фев. 25, 2025

Background/Objectives: Streptococcus pneumoniae (S. pneumoniae) is a major pathogen causing severe infectious diseases, with an escalating issue of antimicrobial resistance that threatens the efficacy existing antibiotics. Given challenges in developing traditional antibiotics, drug repurposing strategies offer novel approach to address crisis. This study aims evaluate antibacterial and anti-biofilm activities approved non-antibiotic anticancer carmofur against multidrug-resistant S. pneumoniae, investigate mechanism action, assess therapeutic potential vivo. Methods/Results: Antimicrobial tests revealed exhibited strong activity strains, minimum inhibitory concentrations (MICs) ranging from 0.25 1 µg/mL. In biofilm detection experiments, not only inhibited formation biofilms, but also effectively removed biofilms under high concentration conditions. Mechanistic studies showed disrupted bacterial membrane permeability decreased intracellular ATP levels. Molecular docking dynamics simulation assays indicated could stably bind thymidylate synthase through hydrogen bonding hydrophobic interactions, thereby exerting effects. Meanwhile, was able repress expression thyA gene at mRNA level. mouse infection model, treatment group reduction approximately two log levels load lung tissue blood, significant decrease inflammatory cytokines TNF-α IL-6, improvement survival rate 60%. Conclusions: summary, demonstrated good anti-infective effects vivo, suggesting its clinical application as agent drug-resistant bacteria.

Язык: Английский

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