Mechanisms of Azole Potentiation: Insights from Drug Repurposing Approaches

ACS Infectious Diseases, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

The emergence of azole resistance and tolerance in pathogenic fungi has emerged as a significant public health concern, emphasizing the urgency for innovative strategies to bolster efficacy azole-based treatments. Drug repurposing stands promising practical avenue advancing antifungal therapy, with potential swift clinical translation. This review offers comprehensive overview synergistic agents uncovered through drug strategies, alongside an in-depth exploration mechanisms by which these augment potency. Drawing from mechanisms, we delineate aimed at enhancing effectiveness, such inhibiting efflux pumps elevate concentrations within fungal cells, intensifying ergosterol synthesis inhibition, mitigating cell azoles, disrupting biological processes extending beyond synthesis. is beneficial development potentiators, it meticulously examines instances provides nuanced discussions on underlying progression potentiators strategies.

Язык: Английский

Inhibitory effects and mode of antifungal action of isobavachalcone on Candida albicans growth and virulence factors

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 179, С. 117352 - 117352

Опубликована: Авг. 28, 2024

The fungus Candida albicans causes various kinds of human infections, including oral thrush, vulvovaginitis and life-endangering bloodstream the incidence which are rising. Worsening this, clinical antifungals limited to a few, highlighting necessity develop novel antifungal therapies. In this study, activities isobavachalcone against C. SC5314 nine isolates were tested. effects (IBC) on virulence factors, such as hyphal formation, adhesion, biofilm formation extracellular phospholipase production, well underlying mechanism, also evaluated. Antifungal susceptibility test revealed that IBC has significant anti-Candida activities, with both MIC MFC being 4-5 μg/mL all strains Hyphal in RPMI-1640, Spider GlcNAc medium, adhesion abiotic polystyrene surfaces A549 cells, could be inhibited by IBC. Most important, inhibit development. PI staining tests showed increase cell membrane permeability, suggesting damages fungal membrane. was further demonstrated induce excessive ROS production planktonic cells its mature biofilms, DCFH fluorescence detection through flowcytometry relative intensity analysis (with microplate reader). roles activity confirmed antioxidant rescue assays tests. Compared activity, cytotoxicity mammalian low, indicating potential developing

Язык: Английский

Extracellular Hsp90 of Candida albicans contributes to the virulence of the pathogen by activating the NF-κB signaling pathway and inducing macrophage pyroptosis

Microbiological Research, Год журнала: 2024, Номер 290, С. 127964 - 127964

Опубликована: Ноя. 5, 2024

Язык: Английский