Antifungal activity of 2-chloro-N-phenylacetamide: a new molecule with fungicidal and antibiofilm activity against fluconazole-resistant Candida spp.

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.

Design of Proteolytic-Resistant Antifungal Peptides by Utilizing Minimum d-Amino Acid Ratios

“…The ability of Candida to form biofilms is also a major obstacle to the drug treatment of fungal infections. − After the formation of biofilms, eradication of infections by antifungal medications becomes challenging. The formation of a biofilm serves as a physical barrier, providing protection to fungal colonies and impeding the infiltration of antifungal drugs .…”

The Antifungal Potential of Niclosamide and Structurally Related Salicylanilides

“…The niclosamide scaffold was meanwhile also successfully replaced by Schiff base and acyl hydrazone bridged antifungals bearing halogenated salicyl moieties [ 109 , 110 ]. The structurally even simpler 2-chloro- N -phenylacetamide has likewise revealed promising activities against Aspergillus and Candida species, including drug-resistant strains, while it exhibited promising DHFR (dihydrofolate reductase) inhibitory and ergosterol-targeting mechanisms of action [ 111 , 112 , 113 , 114 ]. How far these promising modified compounds will have an impact on the development of new antifungals remains to be shown.…”

Resistencia Antimicrobiana

“…Se ha demostrado, además, que la Anfotericina B es altamente efectiva en contra de microorganismos fúngicos del género Cryptococcus y Candida, Quiles y García, mencionan en su artículo que varios estudios multicéntricos han evidenciado cierto grado de resistencia a este fármaco. Señalan que la Candida auris actualmente posee tasas de resistencia entre el 10 al 30%, por otro lado, el género de Trichosporon llega a presentar una resistencia de hasta el 50% a este fármaco (17,18).…”