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.

Breakpoints for the Classification of Anti-Candida Compounds in Antifungal Screening.

INTRODUCTION: The absence of a standardized classification scheme for the antifungal potency of compounds screened against Candida species may hinder the study of new drugs. This systematic review proposes a scheme of interpretative breakpoints for the minimum inhibitory concentration (MIC) of bioactive compounds against Candida species in in vitro tests. MATERIALS AND METHODS: A literature search was conducted in the PubMed, Scopus, Web of Science, Lilacs, and SciFinder databases for the period from January 2015 to April 2020. The following inclusion criterion was used: organic compounds tested by the microdilution technique according to the Clinical and Laboratory Standards Institute protocol against reference strains of the genus Candida. A total of 545 articles were retrieved after removing duplicates. Of these, 106 articles were selected after applying the exclusion criteria and were evaluated according to the number of synthesized molecules and their chemical classes, the type of strain (reference or clinical) used in the antifungal test, the Candida species, and the MIC (in µg/mL) used. RESULTS: The analysis was performed based on the median, quartiles (25% and 75%), maximum, and minimum values of four groups: all strains, ATCC strains, C. albicans strains, and C. albicans ATCC strains. The following breakpoints were proposed to define the categories: MIC < 3.515 µg/mL (very strong bioactivity); 3.516-25 µg/mL (strong bioactivity); 26-100 µg/mL (moderate bioactivity); 101-500 µg/mL (weak bioactivity); 500-2000 µg/mL (very weak bioactivity); and >2000 µg/mL (no bioactivity). CONCLUSIONS: A classification scheme of the antifungal potency of compounds against Candida species is proposed that can be used to identify the antifungal potential of new drug candidates.

Ferulic acid ethyl ester diminished Complete Freund's Adjuvant-induced incapacitation through antioxidant and anti-inflammatory activity.

Ferulic acid ethyl ester (FAEE) is a derivate from ferulic acid which reportedly has antioxidant effect; however, its role on inflammation was unknown. In this study, we investigated the orally administered FAEE anti-inflammatory activity on experimental inflammation models and Complete Freund's Adjuvant (CFA)-induced arthritis in rats. CFA-induced arthritis has been evaluated by incapacitation model and radiographic knee joint records at different observation time. FAEE (po) reduced carrageenan-induced paw edema (p < 0.001) within the 1st to 5th hours at 50 and 100 mg/kg doses. FAEE 50 and 100 mg/kg, po inhibited leukocyte migration into air pouch model (p < 0.001), and myeloperoxidase, superoxide dismutase, and catalase activities (p < 0.001) increased total thiol concentration and decreased the TNF-α and IL-1ß concentrations, NO, and thiobarbituric acid reactive species. In the CFA-induced arthritis, FAEE 50 and 100 mg/kg significantly reduced the edema and the elevation paw time, a joint disability parameter, since second hour after arthritis induction (p < 0.001). FAEE presented rat joint protective activity in radiographic records (p < 0.001). The data suggest that the FAEE exerts anti-inflammatory activity by inhibiting leukocyte migration, oxidative stress reduction, and pro-inflammatory cytokines.