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Fungal infections are responsible for high mortality rates in immunocompromised and high‐risk surgical patients. Therapy failures during the last decades due to increasing multidrug resistance demand innovative strategies for novel and effective antifungal drugs. Synergistic combinations of antifungals with non‐antifungal agents highlight a pragmatic strategy to reduce the development of drug resistance and potentially repurpose known compounds with other functions to bypass costly and time‐consuming novel drug development. [ABSTRACT FROM AUTHOR]

Candida albicans biofilms play a key role in denture stomatitis, one of the most common oral pathologies in elderly people. Because biofilms are highly resistant to antifungals, new pharmacological strategies are needed. Aspirin and nitric oxide-donor molecules have both shown antibiofilm effects on C. albicans, making them promising candidates for treatment. In this study, we evaluated the antifungal/antibiofilm effect of a nitric-oxide releasing aspirin (NO-ASA) on C. albicans isolates from denture stomatitis patients in vitro. Disk diffusion assays showed that while NO-ASA had no antifungal effect, the drug potentiated fluconazole inhibition zone diameters, increasing the effect of fluconazole by 20–30% (p<0.05). The effect of NO-ASA on the morphogenesis of C. albicans was evaluated using light microscopy after inducing hyphae formation. For all clinical strains assayed, 125 μM NO-ASA significantly decreased the number of filamentous cells present (p<0.01). Adhesion to abiotic surfaces, a critical event for biofilm formation, was evaluated in 96-well polystyrene plates using crystal violet assay; 125 μM NO-ASA significantly inhibited adhesion. Biofilms were observed with scanning electron microscopy (SEM) and quantified using XTT reduction assay. NO-ASA decreased biofilm formation (IC50 ranging from 300 μM to 700 μM), consistent with SEM findings of altered biofilm microarchitecture. PGE2 and carboxy-PTIO (an NO scavenger) both blocked the antibiofilm effects of NO-ASA, suggesting that the efficacy of NO-ASA may be associated with both inhibition of PGE2 synthesis and release of NO. NO-ASA is a promising novel antibiofilm agent for treating fluconazole-resistant strains of C. albicans. [ABSTRACT FROM AUTHOR]

Background: Chrysobalanus icaco is a medicinal plant commonly used to treat fungal infections in Brazilian Amazonian region. Objective: This work aimed to evaluate the antifungal activity of the hydroalcoholic extract of C. icaco (HECi) against oral clinical isolates of Candida spp. and to determine the pharmacognostic parameters of the herbal drug and the phytochemical characteristics of HECi. Materials and Methods: The pharmacognostic characterization was performed using pharmacopoeial techniques. Phytochemical screening, total flavonoid content, and high-performance liquid chromatography (HPLC) analysis were used to investigate the chemical composition of the HECi. A broth microdilution method was used to determine the antifungal activity of the extract against 11 oral clinical isolates of Candida spp. Results: Herbal drug presented parameters which were within the limits set forth in current Brazilian legislation. A high amount of flavonoid content (132,959.33 ± 12,598.23 µg quercetin equivalent/g of extract) was found in HECi. Flavonoids such as myricetin and rutin were detected in the extract by HPLC analyses. HECi showed antifungal activity against oral isolates of Candida albicans and Candida parapsilosis (minimum inhibitory concentrations [MIC] 3.12 and 6.25 mg/mL, respectively), and C. albicans American American Type Culture Collection (MIC <1.56 mg/mL). Conclusion: HECi was shown to possess antifungal activity against Candida species with clinical importance in the development of oral candidiasis, and these activities may be related to its chemical composition. The antifungal activity detected for C. icaco against Candida species with clinical importance in the development of oral candidiasis can be attributed to the presence of flavonoids in HECi, characterized by chromatographic and spectroscopic techniques. [ABSTRACT FROM AUTHOR]

Candida albicans is the primary cause of systemic candidiasis, which has a high mortality rate. Unfortunately, the number of antifungal drugs available for treatment of Candida infections is limited, and there is an urgent need for development of new drugs and alternative therapeutic options. We investigated the combinatory effect of fluconazole (FLCZ) and 640 FDA-approved drugs in vitro. Ten drugs enhanced and 77 drugs attenuated the antifungal activity of FLCZ. Other drugs did not appear to alter the antifungal activity of FLCZ, although 17 drugs displayed potency equivalent to or greater than that of FLCZ. The 10 FLCZ-enhancing drugs included three inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA reductase, whose synergistic activity had been reported previously. However, the antifungal effects of 3 FLCZ enhancers—artesunate, carvedilol, and bortezomib—were previously unknown. In addition, many drugs were found to attenuate the antifungal activity of FLCZ, including 17 cyclooxygenase (COX) inhibitors, 15 estrogen-related agents, vitamin A- and D-related compounds, antihypertensive drugs, and proton pump inhibitors. Although the clinical significance remains to be determined, analyses of molecular events responsible for synergy or antagonism could provide insight into more efficient use of existing antifungals and lead to novel therapies. [ABSTRACT FROM AUTHOR]

Background: Asaronaldehyde (2, 4, 5-trimethoxybeznaldehyde) is an active component of Acorus gramineus rhizome. This study aims to evaluate the anti-Candida efficacy of asaronaldehyde and its three structural isomers, namely, 2, 3, 4-trimethoxybenzaldehyde, 3, 4, 5-trimethoxybenzaldehyde, and 2, 4, 6- trimethoxybenzaldehyde. Methods: Susceptibility testing of test compounds was carried out using standard methodology (M27-A2) as per clinical and laboratory standards institute guidelines. Minimum fungicidal concentration (MFC) was determined as the lowest concentration of drug killing 99.9% of Candida cells. The effect on sterol profile was evaluated using the ergosterol quantitation method. Effects on morphogenesis, adhesion and biofilm formation in C. albicans were studied using germ-tube, adherence and biofilm formation assays respectively. Cytotoxicity of test compounds to human RBCs was determined by hemolysis assay. Results: 2, 4, 6-Trimethoxybenzaldehyde exhibited significant anti-Candida activity (P = 0.0412). Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were established as 0.25 and 0.5 mg/mL, respectively. All of the test compounds showed significant inhibition of hyphal form transition in yeast at MIC/2 and MIC/4 values. 3, 4, 5-Trimethoxybenzaldehyde and 2, 4, 6-trimethoxybenzaldehyde inhibited adhesion and biofilms. A hemolytic assay of these compounds revealed that they were non-toxic at MIC values. Asaronaldehyde reduced sterol content. Conclusion: Asaronaldehyde and 2, 4, 6-trimethoxybenzaldehyde showed anti-Candida efficacy. [ABSTRACT FROM AUTHOR]