Antifungal activity and mechanism of action of 2-chloro-N -phenylacetamide: a new molecule with activity against strains of Aspergillus flavus

Abstract

Aspergillus genus causes many diseases, and the species Aspergillus fl avus is highly virulent. Treatment of aspergillosis involves azole derivatives such as voriconazole and polyenes such as amphotericin B. Due to an increase in fungal resistance, treatments are now less effective; the search for new compounds with promising antifungal activity has gained importance. The aims of this study were to evaluate the effects of the synthetic amide 2-chloro-N-phenylacetamide (A 1 Cl) against strains of Aspergillus fl avus and to elucidate its mechanism of action. Thus, the minimum inhibitory concentration, minimum fungicidal concentration, conidial germination, associations with antifungal agents, cell wall activities, membrane activities and molecular docking were evaluated.A 1 Cl presented antifungal activity against Aspergillus fl avus strains with a minimum inhibitory concentration of between 16 and 256 μg/mL and a minimum fungicidal concentration between 32 and 512 μg/mL. The minimum inhibitory concentration of A 1 Cl also inhibited conidial germination, but when associated with amphotericin B and voriconazole, it promoted antagonistic effects. Binding to ergosterol on the fungal plasma membrane is the likely mechanism of action, along with possible inhibition of DNA synthesis through the inhibition of thymidylate synthase. It is concluded that the amide 2-chloro-N-phenylacetamide has promising antifungal potential.

α-Pinene: Docking Study, Cytotoxicity, Mechanism of Action, and Anti-Biofilm Effect against Candida albicans

“…There are no previous studies reporting the interaction of α-pinene with the tested enzymes. In the study, the α-pinene-thymidylate synthase interaction presented the lowest binding energy, leading to a prediction that the phytoconstituent has the ability to bind to this receptor with consequent activity involving fungal-DNA synthesis [ 21 ].…”

Residual effect of commonly used fungicides in strawberries on Amblyseius swirskii, Neoseiulus cucumeris, and Neoseiulus californicus (Mesostigmata: Phytoseiidae)

“…Additionally, the oxidative capabilities of hydrogen peroxide would avertedly allow it to interact with critical biomolecules such as nucleic acids, proteins, and lipids (Shi et al 2022) in the cuticle of many arthropods, which could also explain the reduced predatory mite survival over time. Phenylacetamides represented by cyflufenamid have been demonstrated to inhibit DNA synthesis through the inhibition of thymidylate synthase (Ferreira et al 2021). Despite the fact that residues of cyflufenamid have been reported to be safe for bees (Piechowicz et al 2022) our results indicate that they negatively affect predatory mites.…”

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.…”