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Candidiasis is one of the most frequent nosocomial infections affecting an increasing number of at-risk patients. Candida albicans remains the most frequent causative agent of candidiasis, but, in the last decade, C. auris has emerged as a formidable multi-drug-resistant pathogen. Both species are fully capable of forming biofilms, which contribute to resistance, increasing the urgency for new effective antifungal therapies. Repurposing existing drugs could significantly accelerate the development of novel therapies against candidiasis. Here, we have screened the Repurposing Hub library from the Broad Institute, containing over 6000 compounds, in search for inhibitors of C. albicans and C. auris biofilm formation. The primary screen identified 57 initial hits against C. albicans and 33 against C. auris. Confirmatory concentration-dependent assays were used to validate the activity of the initial hits and, at the same time, establish their anti-biofilm potency. Based on these results, ebselen, temsirolimus, and compound BAY 11-7082 emerged as the leading repositionable compounds. Subsequent experiments established their spectrum of antifungal activity against yeasts and filamentous fungi. In addition, their in vivo activity was examined in the murine models of hematogenously disseminated C. albicans and C. auris infections. Although promising, further in vitro and in vivo studies are needed to confirm their potential use for the therapy of candidiasis and possibly other fungal infections.

Byrsonima intermedia is a species of bush popularly used to treat gastrointestinal disorders, such as gastric ulcers, gastritis, and diarrhea. Previous studies have revealed that the methanolic crude extract of B. intermedia leaves has gastroprotective and healing properties. In this new study, we specifically investigated two purified partitions, ethyl acetate (EtOAc) and water (AcoAq), obtained from the crude extract to characterize the antiulcer effects of these two partitions and the mechanisms of action of this medicinal plant. The healing effects of these partitions on the gastric and duodenal mucosa were assessed after ischemia-reperfusion (I/R) or acetic acid-induced injury. The involvement of tumor necrosis factor-alpha (TNF-alpha), interleukin 1β (IL-1β), interleukin 10 (IL-10), and myeloperoxidase (MPO) activity and glutathione (GSH) levels were determined. The antibacterial activity against Helicobacter pylori was evaluated using microdilution methods. The phytochemical analysis of AcoAq revealed a predominance of oligomeric proanthocyanidins and galloyl quinic esters, whereas EtOAc was found to contain concentrated flavonoids. Both partitions led to a significant reduction in gastric lesions, but AcoAq was more effective than EtOAc with regard to anti-Helicobacter pylori activity in addition to protecting the gastric mucosa against ethanol, non-steroidal anti-inflammatory drugs (NSAIDs) and duodenal mucosal damage induced by cysteamine.Additionally, both partitions were associated with a significant increase in gastric and duodenal healing and increased gastric mucosal GSH content after damage induced by acetic acid. On the other hand, after 6 days of treatment, EtOAc was more effective than AcoAq in ameliorating gastric damage upon initiation of the gastric I/R, which was accompanied by a significant reduction in the activity of gastric mucosal MPO, IL 1-β and TNF-alpha, as well as an elevation in IL-10 and GSH content. These results demonstrate that the oligomeric proanthocyanidins and galloyl quinic esters present in AcoAq were more effective in the prevention of gastric and duodenal ulcers due to the antioxidant effects of these compounds, whereas the flavonoids present in EtOAc were more effective due to their anti-inflammatory activity on the gastric and duodenal tissue. All these results confirm that the rich phytochemical diversity of B. intermedia contributes to the pharmacological actions of this medicinal plant on the gastrointestinal tract in addition to its activity against H. pylori.

We have previously reported on the activity of different extracts from Astronium sp. against Candida albicans, with the hydroethanolic extract prepared from leaves of A. urundeuva, an arboreal species widely distributed in arid environments of South America and often used in folk medicine, displaying the highest in vitro activity. Here we have further evaluated the antifungal activity of this extract against strains of C. albicans and C. glabrata, the two most common etiological agents of candidiasis. The extract was tested alone and loaded into a nanostructured lipid system (10% oil phase, 10% surfactant and 80% aqueous phase, 0.5% Poloxamer 407®). In vitro susceptibility assays demonstrated the antifungal activity of the free extract and the microemulsion against both Candida species, with increased activity against C. glabrata, including collection strains and clinical isolates displaying different levels of resistance against the most common clinically used antifungal drugs. Checkerboard results showed synergism when the free extract was combined with amphotericin B against C. albicans. Serial passage experiments confirmed development of resistance to fluconazole but not to the free extract upon prolonged exposure. Although preformed biofilms were intrinsically resistant to treatment with the extract, it was able to inhibit biofilm formation by C. albicans at concentrations comparable to those inhibiting planktonic growth. Cytotoxicity assays in different cell lines as well as an alternative model using Artemia salina L. confirmed a good safety profile of the both free and loaded extracts, and an in vivo assay demonstrated the efficacy of the free and loaded extracts when used topically in a rat model of vaginal candidiasis. Overall, these results reveal the promise of the A. urundeuva leaves extract to be further investigated and developed as an antifungal.

Herbal-loaded drug delivery nanotechnological systems have been extensively studied recently. The antimicrobial activity of medicinal plants has shown better pharmacological action when such plants are loaded into a drug delivery system than when they are not loaded. Syngonanthus nitens Bong. (Rhul.) belongs to the Eriocaulaceae family and presents antiulcerogenic, antioxidant, antibacterial, and antifungal activity. The aim of this study was to evaluate the antifungal activity of Syngonanthus nitens (S. nitens) extract that was not loaded (E) or loaded (SE) into a liquid crystal precursor system (S) for the treatment of vulvovaginal candidiasis (VVC) with Candida albicans. The minimal inhibitory concentration (MIC) was determined by the microdilution technique. Additionally, we performed hyphae inhibition and biofilm tests. Finally, experimental candidiasis was evaluated in in vivo models with Wistar female rats. The results showed effective antifungal activity after incorporation into S for all strains tested, with MICs ranging from 31.2 to 62.5 μg/mL. Microscopic observation of SE revealed an absence of filamentous cells 24 h of exposure to a concentration of 31.2 μg/mL. E demonstrated no effective action against biofilms, though SE showed inhibition against biofilms of all strains. In the in vivo experiment, SE was effective in the treatment of infection after only two days of treatment and was more effective than E and amphotericin B. The S. nitens is active against Candida albicans (C. albicans) and the antifungal potential is being enhanced after incorporation into liquid crystal precursor systems (LCPS). These findings represent a promising application of SE in the treatment of VVC.