8-Hydroxyquinoline-5-sulfonamides are promising antifungal candidates for the topical treatment of dermatomycosis.

AIM: The purpose of this study was to uncover insights into the mechanism of action of the 8-hydroxyquinoline derivatives PH151 and PH153. In addition, with the future perspective of developing a topical drug for the treatment of candidiasis and dermatophytosis, the antifungal activity of a nanoemulsion formulation containing the most active compound (PH151) is also presented here. METHODS AND RESULTS: Sorbitol protection assay and scanning electron microscopy indicate that the 8-hydroxyquinoline derivatives act on the cell wall of Candida sp. and dermatophytes and they inhibit the pseudohyphae formation of C. albicans. These findings demonstrate a strong effect of these compounds on C. albicans morphogenesis, which can be considered a potential mode of action for this molecule. Besides, the nanoemulsion formulation MIC values ranged from 0·5 to 4 µg ml-1 demonstrating the significant antifungal activity when incorporated into a pharmaceutical formulation. CONCLUSIONS: Taken together, the results support the potential of these molecules as promising antifungal candidates for the treatment of candidiasis and dermatophytosis. SIGNIFICANCE AND IMPACT OF THE STUDY: There is an emerging need to fill the pipeline with new antifungal drugs due to the limitations presented by the currently used drugs. In this study, we have described a novel formulation with a 8-hydroxyquinoline-5-sulfonamide derivative which has presented a great potency in providing a finished product. Furthermore, the derivative has shown a selective mechanism of action confirming its potential to be developed into a new drug candidate.

In vitro evaluation of the acquisition of resistance, antifungal activity and synergism of Brazilian red propolis with antifungal drugs on Candida spp.

AIMS: To evaluate the ability of Candida parapsilosis and Candida glabrata to develop phenotypic resistance to a benzophenone enriched fraction obtained from Brazilian red propolis (BZP-BRP) as compared to fluconazole (FLC). To investigate possible synergy between BZP-BRP and FLC and anidulafungin (AND). METHODS AND RESULTS: To analyse the development of resistance, isolates susceptible to these antifungals were cultured in increasing concentrations of FLC and BZP-BRP. The increase in FLC minimum inhibitory concentration for all isolates was evident and the majority developed resistance, whereas none isolated became less susceptible to BZP-BRP. Synergism was investigated by checkerboard method. BZP-BRP demonstrated synergy with FLC and indifference with AND for most isolates. CONCLUSIONS: In conclusion, the synergism observed with FLC suggests that BZP-BRP could be a possible therapeutic strategy for the treatment of infections related to FLC-resistant Candida sp. SIGNIFICANCE AND IMPACT OF THE STUDY: The indiscriminate use of antifungals results in the emergence of drug-resistant strains among previously susceptible populations. BZP-BRP can become an alternative for the treatment of persistent infections caused by Candida sp.