Butyl isothiocyanate exhibits antifungal and anti-biofilm activity against Candida albicans by targeting cell membrane integrity, cell cycle progression and oxidative stress.

The prevalence of Candida albicans infection has increased during the past few years, which contributes to the need for new, effective treatments due to the increasing concerns regarding antifungal drug toxicity and multidrug resistance. Butyl isothiocyanate (butylITC) is a glucosinolate derivative, and has shown a significant antifungal effect contrary to Candida albicans. Additionally, how butylITC affects the virulence traits of C. albicans and molecular mode of actions are not well known. Present study shows that at 17.36 mM concentration butylITC inhibit planktonic growth. butylITC initially slowed the hyphal transition at 0.542 mM concentration. butylITC hampered biofilm development, and inhibits biofilm formation at 17.36 mM concentration which was analysed using metabolic assay (XTT assay) and Scanning Electron Microscopy (SEM). In addition, it was noted that butylITC inhibits ergosterol biosynthesis. The permeability of cell membranes was enhanced by butylITC treatment. Moreover, butylITC arrests cells at S-phase and induces intracellular Reactive Oxygen Species (ROS) accumulation in C. albicans. The results suggest that butylITC may have a dual mode of action, inhibit virulence factors and modulate cellular processes like inhibit ergosterol biosynthesis, cell cycle arrest, induces ROS production which leads to cell death in C. albicans.

Hydroxychloroquine an Antimalarial Drug, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Multitargeting.

Candida albicans is the primary etiological agent associated with candidiasis in humans. Unrestricted growth of C. albicans can progress to systemic infections in the worst situation. This study investigates the antifungal activity of Hydroxychloroquine (HCQ) and mode of action against C. albicans. HCQ inhibited the planktonic growth and yeast to hyphal form morphogenesis of C. albicans significantly at 0.5 mg/ml concentration. The minimum inhibitory concentrations (MIC50) of HCQ for C. albicans adhesion and biofilm formation on the polystyrene surface was at 2 mg/ml and 4 mg/ml respectively. Various methods, such as scanning electron microscopy, exploration of the ergosterol biosynthesis pathway, cell cycle analysis, and assessment of S oxygen species (ROS) generation, were employed to investigate HCQ exerting its antifungal effects. HCQ was observed to reduce ergosterol levels in the cell membranes of C. albicans in a dose-dependent manner. Furthermore, HCQ treatment caused a substantial arrest of the C. albicans cell cycle at the G0/G1 phase, which impeded normal cell growth. Gene expression analysis revealed upregulation of SOD2, SOD1, and CAT1 genes after HCQ treatment, while genes like HWP1, RAS1, TEC1, and CDC 35 were downregulated. The study also assessed the in vivo efficacy of HCQ in a mice model, revealing a reduction in the pathogenicity of C. albicans after HCQ treatment. These results indicate that HCQ holds for the development of novel antifungal therapies.

Ethyl Isothiocyanate as a Novel Antifungal Agent Against Candida albicans.

In the recent years, occurrence of candidiasis has increased drastically which leads to significant mortality and morbidity mainly in immune compromised patients. Glucosinolate (GLS) derivatives are reported to have antifungal activities. Ethyl isothiocyanate (EITC) and its antifungal activity and mechanism of action is still unclear against Candida albicans. The present work was designed to get a mechanistic insight in to the anti-Candida efficacy of EITC through in vitro and in vivo studies. EITC inhibited C. albicans planktonic growth at 0.5 mg/ml and virulence factors like yeast to hyphal form morphogenesis (0.0312 mg/ml), adhesion to polystyrene surface (0.0312 mg/ml) and biofilm formation (developing biofilm at 2 mg/ml and mature biofilm at 0.5 mg/ml) effectively. EITC blocked ergosterol biosynthesis and arrested C. albicans cells at S-phase. EITC caused ROS-dependent cellular death and nuclear or DNA fragmentation. EITC at 0.0312 mg/ml concentration regulated the expression of genes involved in the signal transduction pathway and inhibited yeast to hyphal form morphogenesis by upregulating TUP1, MIG1, and NRG1 by 3.10, 5.84 and 2.64-fold, respectively and downregulating PDE2 and CEK1 genes by 15.38 and 2.10-fold, respectively. EITC has showed haemolytic activity at 0.5 mg/ml concentration. In vivo study in silk worm model showed that EITC has toxicity to C. albicans at 0.5 mg/ml concentration. Thus, from present study we conclude that EITC has antifungal activity and to reduce its MIC and toxicity, combination study with other antifungal drugs need to be done. EITC and its combinations might be used as alternative therapeutics for the prevention and treatment of C. albicans infections.