Anticandidal activity of hetero-dinuclear copper(II) Mn(II) Schiff base and its potential action of the mechanism

Invasive fungal infections are one of the major challenges especially for immunosuppressed patients since they are drug resistant and pathogen to patients. Therefore, developing new, efficient and nonresistant antifungal agents have been a primary focus of international research. In the current study, a novel Schiff base hetero-dinuclear copper(II) Mn(II) complex] (SB) derivative was investigated for its anticandidal activity against Candida albicans and possible mechanisms inducing cell death. The results revealed that SB treatment induces apoptotic and necrotic pathways in C. albicans ATCC10231 strain. Intracellular reactive oxygen species production determined by 2′,7′-dichlorofluorescein diacetate staining was triggered by SB and amphotericin B administrations in a dose-dependent manner. Gene expression analysis demonstrated that SB exposure resulted in regulation of critical development and stress related gene expressions. SB treatment directly upregulated expression of stress related genes, DDR48 and RIM101, while suppressed important cell signaling and antibiotic resistance acquiring related genes such as HSP90, ERG11 and EFG1. Furthermore, CaMCA1 mRNA levels were found to be significantly high in SB-treated yeast cells, indicating possible caspase-like mechanism activation. Scanning electron microscopy analysis confirmed that SB treatment led to severe cell wall integrity disruption and wrinkling. The study will encourage development of SB-based anticandidal regimens but further studies are highly warranted to understand limitations and the extended use in the routine.