Inhibition of apoptosis and biofilm formation in Candida auris by click-synthesized triazole-bridged quinoline derivatives.

Candida auris , a recent addition to the Candida species, poses a significant threat with its association to numerous hospital outbreaks globally, particularly affecting immunocompromised individuals. Given its resistance to existing antifungal therapies, there is a pressing need for innovative treatments. In this study, novel triazole bridged quinoline derivatives were synthesized and evaluated for their antifungal activity against C. auris . The most promising compound, QT7, demonstrated exceptional efficacy with a minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of 0.12 μg mL -1 and 0.24 μg mL -1 , respectively. Additionally, QT7 effectively disrupted mature biofilms, inhibiting them by 81.98% ± 8.51 and 89.57 ± 5.47 at MFC and 2× MFC values, respectively. Furthermore, QT7 induced cellular apoptosis in a dose-dependent manner, supported by various apoptotic markers such as phosphatidylserine externalization, mitochondrial depolarization, and reduced cytochrome c and oxidase activity. Importantly, QT7 exhibited low hemolytic activity, highlighting its potential for further investigation. Additionally, the physicochemical properties of this compound suggest its potential as a lead drug candidate, warranting further exploration in drug discovery efforts against Candida auris infections.