Metal tungstates as antifungal and antibiofilm agents againstCandida albicans.

Multidrug-resistant fungal infections caused by Candida albicans, particularly those associated with biofilm formation and virulence, represent a growing clinical challenge and demand alternative antifungal strategies beyond conventional drugs. In this study, we investigated ultrasonically synthesized metal tungstates as antifungal and antibiofilm agents against multi-azole-resistant C. albicans. A series of metal tungstates (AgWO4, BaWO4, CaWO4, CoWO4, MnWO4, and ZnWO4) were synthesized via sonication. This yielded phase-pure microstructures with distinct morphologies, homogeneous elemental distribution, and high crystallinity. Comparative screening against multiple Candida species revealed AgWO4 as the most potent antifungal material. It showed fungicidal activity at 5 µg/ml and exhibited 93% biofilm inhibition and altered hyphal morphogenesis at 0.5 µg/ml. ZnWO4 displayed 97% biofilm inhibition and antifungal activity at 300 µg/ml, whereas other tungstates showed minimal biological effects. Mechanistic studies demonstrated that AgWO4 and ZnWO4 increased intracellular ROS production and decreased metabolic activity, accompanied by alterations in fungal morphology. Notably, AgWO4 displayed additive interactions with conventional antifungal drugs and showed no resistance development during serial passaging for 15 days. Toxicity assessments using plant, nematode, blood cell, and liver cell line models confirmed favorable biocompatibility within antifungally effective concentration ranges. ZnWO4 showed lower toxicity than AgWO4, with IC50 values of 5193 and 63 µg/ml against HepG2 cells. Overall, this work establishes AgWO4 and ZnWO4 as antivirulence-oriented, resistance-mitigating antifungal materials for combating persistent, drug-resistant fungal infections.