Increasing Susceptibility of Drug-Resistant to Fluconazole and Terbinafine by 2(5)-Furanone Derivative.

The frequency of mycoses caused by drug-resistant fungal pathogen has increased drastically over the last two decades. The spread of drug-resistant strains, along with the limitations of currently available antifungals, complicates the management of fungal infections, thereby representing great challenges for clinical healthcare. Among various antimicrobial pharmacophores, 2(5)-furanone derivatives have demonstrated antimicrobial, antifungal, and antibiofilm activities. In this study, we report the antifungal activity of the 2(5)-furanone derivative , consisting of three pharmacophores, namely chlorinated 2(5)-furanone, sulfonyl group, and -menthol moiety. Although exhibiting moderate antifungal activity alone with the minimum inhibitory concentration (MIC) values of 32-256 μg/mL, potentiates the activity of fluconazole and terbinafine with fractional inhibitory concentration index (FICI) values of 0.27-0.50. Thus, 16 μg/mL of reduced the MICs of these antifungals against fluconazole-resistant isolates four-fold, achieving similar values as for the intermediately susceptible phenotype. Confocal laser scanning microscopy revealed that the fluorescent 2(5)-furanone derivative was also able to penetrate through biofilms formed by . Indeed, in the presence of , even sub-MIC concentrations of both fluconazole and terbinafine led to significant reduction of CFUs in the mature biofilm. Thus, appears to be a promising candidate for the development of novel antifungal agents as well as enhancers of current antifungal agents, particularly for the treatment of drug-resistant infections.