Abstract
In the current context of emerging drug-resistant fungal pathogens such as Candida albicans and Candida parapsilosis, discovery of new antifungal agents is an urgent matter. This research aimed to evaluate the antifungal potential of 2-chloro-N-phenylacetamide against fluconazole-resistant clinical strains of C. albicans and C. parapsilosis. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), inhibition of biofilm formation and its rupture, sorbitol and ergosterol assays, and association between this molecule and common antifungal drugs, amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 µg.mL-1, and a MFC of 512-1,024 µg.mL-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. 2-chloro-N-phenylacetamide did not promote antifungal activity through binding to cellular membrane ergosterol nor it damages the fungal cell wall. Antagonism was observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal activity by inhibiting both planktonic cells and biofilm of fluconazole-resistant strains. Its combination with other antifungals should be avoided and its mechanism of action remains to be established.
Highlights
In the current context of emerging drug-resistant fungal pathogens such as Candida albicans and Candida parapsilosis, discovery of new antifungal agents is an urgent matter
The 2-chloro-N-phenylacetamide antifungal profile was evaluated through minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) determinations
The MIC and MFC results together with the microbial growth curves reveal that 2-chloro-N-phenylacetamide presents inhibitory activity against strains of C. albicans, Table 3
Summary
In the current context of emerging drug-resistant fungal pathogens such as Candida albicans and Candida parapsilosis, discovery of new antifungal agents is an urgent matter. C. albicans remains the most common fungal pathogen worldwide, a significant increase in infections caused by non-albicans species is reported in the last decade (Jain et al, 2017; Lamoth et al, 2018; Vieira et al, 2018). Of such species, C. parapsilosis has already been ranked as the second most frequent cause of candidemia in some countries of Southern Europe, Africa, North America and, notably, in a great portion of South America, especially in neonates, transplant recipients and patients with other malignancies such as cancer (Silva et al, 2012; Sun et al, 2019; Tóth et al, 2019; Zupančič et al, 2018)
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