Aline Jacobi Dalla Lana

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

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).

Synthesis of isosteric triterpenoid derivatives and antifungal activity.

Dermatomycoses are among the most widespread and common superficial and cutaneous fungal infections in humans. There is an urgent need to develop efficient and non‐toxic antimycotic agents with a specific spectrum of activity. Triterpenes have been demonstrated to exhibit a wide range of biological activities, including antifungal activities. In this study, through hemisynthesis, we aimed to obtain triterpene‐isosteric molecules from betulinic and ursolic acids to improve the antifungal activity and spectrum of action of these compounds. Six compounds were resynthesized and tested against eleven mucocutaneous and cutaneous mycotic agents. The results of the susceptibility assays were expressed as the minimal inhibitory concentration (MIC). The MIC values of the piperazinyl derivatives of ursolic and betulinic acids that were active against pathogenic yeasts were in the range of 16–32 μg/mL and 4–16 μg/mL, respectively, whereas fungicidal effects were observed at concentrations ranging from 16 to 128 μg/mL and 8 to 128 μg/mL, respectively. The piperazinyl derivative of betulinic acid exhibited an antifungal profile similar to that of terbinafine and was the most effective derivative against dermatophytes. This strategy led to a promising candidate for the development of a new antifungal agent.

In vitro synergism of a water insoluble fraction of Uncaria tomentosa combined with fluconazole and terbinafine against resistant non-Candida albicans isolates

Abstract Context: Uncaria tomentosa D.C. (Rubiaceae) has several biological activities, including activity against resistant Candida strains. The synergistic interaction with terbinafine or fluconazole can be an important alternative to overcome this resistance. Objectives: The potential synergy between a water insoluble fraction (WIF) from Uncaria tomentosa bark and the antifungals terbinafine (TRB) and fluconazole (FLZ) against non-Candida albicans resistant strains was investigated. Materials and methods: TRB and FLZ, alone and combined with WIF, were tested by the checkerboard procedure using the micro-dilution technique against seven isolates of Candida glabrata and C. krusei. The molecular interactions occurring outside the cell wall were evaluated by scanning electron microscopy, Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC) analysis. Results: The checkerboard inhibitory assay demonstrated synergy for WIF:TRB and WIF:FLZ combinations, respectively. The best synergistic cell damage was demonstrated unequivocally for the associations of WIF and TRB (1.95:4.0 μg/mL) and WIF and FLZ (1.95:8.0 μg/mL). The comparison of the FT-IR spectra of the antifungal alone, and in combination with WIF, allows recognizing clear differences in 3000, 1600, 1400, and 700–800 cm−1 bands. Additionally, modifications on TRB and FLZ thermograms were clearly noticed after their combination with WIF. Conclusions: DSC and infrared analysis demonstrated intermolecular interactions between WIF and either TRB or FLZ. Hence, quite likely the synergistic effect is related to interaction events occurring outside the cell wall between antifungal and cat’s claw proanthocyanidins. A direct action on the cell wall is suggested, without connection with the ABC efflux pump mechanism.