Antifungal Activity, Mode of Action, and Cytotoxicity of 4-Chlorobenzyl p-Coumarate: A Promising New Molecule.

Fungal infections represent a serious health problem worldwide. The study evaluated the antifungal activity of 4-chlorobenzyl p-coumarate, an unprecedented semi-synthetic molecule. Docking molecular and assay experiments were conducted to determine the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC), mode of action, effect on growth, fungal death kinetics, drug association, effects on biofilm, micromorphology, and against human keratinocytes. The investigation included 16 strains of Candida spp, including C. albicans, C. krusei, C. glabrata, C. tropicalis, C. dubliniensis, C. lusitaniae, C. utilis, C. rugosa, C. guilhermondi, and C. parapsilosis. Docking analysis predicted affinity between the molecule and all tested targets. MIC and MFC values ranged from 3.9 µg/mL (13.54 µM) to 62.5 µg/mL (217.01 µM), indicating a probable effect on the plasma membrane. The molecule inhibited growth from the first hour of testing. Association with nystatin proved to be indifferent. All concentrations of the molecule reduced fungal biofilm. The compound altered fungal micromorphology. The tested compound exhibited an IC50 of 7.90±0.40 µg/mL (27.45±1.42 µM) for keratinocytes. 4-chlorobenzyl p-coumarate showed strong fungicidal effects, likely through its action on the plasma membrane and alteration of fungal micromorphology, and mildly cytotoxic to human keratinocytes.

Derivative of 7-hydroxycoumarin has antifungal potential against Candida species and low cytotoxicity against human cells: In silico studies and biological evaluation.

This study investigates the antifungal and cytotoxic properties of 7-(pentyloxy)-2H-chromen-2-one. Through molecular docking and dynamics simulations, we explored the compound's interactions with fungal cell protein targets. Notably, it exhibited strong affinities for 1,3ß-glucan synthase, squalene epoxidase, δ-14-sterol reductase, 14-α-demethylase, and thymidylate synthase, with binding energies ranging from -100.39 to -73.15 kcal/mol. Molecular dynamics simulations confirmed its stable binding at active targets. The MIC and MFC values ranged from 67.16 µM (15.6 µg/mL) to 537.28 µM (125.0 µg/mL). The compound displayed promising antifungal effects, inhibiting fungal growth for at least 24 hours. Fungal plasma membrane function alteration likely contributed to these antifungal mechanisms. Additionally, the combination of the compound with nystatin, fluconazole, and caspofungin showed indifferent effects on antifungal activity. Cytotoxicity assessment in human keratinocyte cells (HaCaT) revealed an IC50 of 100 µM, which was approximately 1.5 times higher than the MIC for C. krusei. Thus, the compound exhibited strongly in silico and in vitro antifungal activity with low cytotoxicity in HaCaT cells. These findings support its potential as a candidate for further development as an antifungal compound.