Open AccessArticle
by 
,,,,, and
Francesco Petrillo
1,†,Annalisa Buonanno
2,†,Angela Maione
2,*,Luigi Longobardo
3,Michele Reibaldi
1,Emilia Galdiero
2,Armando Zarrelli
3,* andMarco Guida
21
Department of Ophthalmology, “City of Health and Science” Hospital, 10126 Turin, Italy
2
Department of Biology, University of Naples Federico II, 80126 Naples, Italy
3
Department of Chemical Science, University of Napoli Federico II, Via Cinthia 4, 80126 Napoli, Italy
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Antibiotics 2026, 15(6), 597; https://doi.org/10.3390/antibiotics15060597
Submission received: 21 April 2026 / Revised: 8 June 2026 / Accepted: 10 June 2026 / Published: 11 June 2026
(This article belongs to the Special Issue The Discovery of Novel Antimicrobial Agents to Combat Infections)
Abstract
Background: Fungal ocular infections, including keratitis and endophthalmitis, remain difficult to treat due to limited antifungal efficacy, poor tissue penetration, and biofilm-mediated resistance. This study evaluated the antifungal and host-protective potential of N-(4-methoxycinnamoyl)-anthranilic acid (NMCA) against Candida albicans and the multidrug-resistant Candidozyma auris. Methods: The antifungal activity of NMCA was assessed by analyzing fungal viability over time, ergosterol levels, and its interaction with fluconazole. Its antibiofilm activity was evaluated through biomass and metabolic activity measurements, together with the expression of genes involved in adhesion (ALS3, ALS5, HWP1) and membrane homeostasis (ERG11, OLE1). In addition, infected epithelial models were used to investigate epithelial damage, intracellular fungal burden, oxidative stress, and wound closure. Results: NMCA showed promising antifungal activity (MIC80 75 μg mL−1 against C. albicans and 100 µg mL−1 against C. auris), inducing a time-dependent reduction in fungal viability of about 4-log10 after 24 h. The compound also reduced ergosterol levels and showed synergistic interaction with fluconazole, as indicated by FICI values of 0.203 for C. albicans and 0.375 for C. auris. Moreover, NMCA markedly inhibited biofilm formation by reducing both biomass and metabolic activity up to approximately 80%, while modulating the expression of key adhesion- and membrane-related genes. Beyond its direct antifungal effects, NMCA reduced epithelial damage and intracellular fungal burden, attenuated oxidative stress, and significantly improved wound closure (reaching 76.26% and 90.46% closure in C. albicans- and C. auris-infected cells, respectively) in infected epithelial models. Conclusions: Although limited by the use of in vitro systems, these findings highlight the multifunctional profile of NMCA, which combines antifungal, antibiofilm, and tissue-protective activities. By simultaneously targeting pathogen viability, biofilm formation, and host cell integrity, NMCA appears to be a promising adjunctive candidate for the treatment of ocular fungal infections, where both pathogen eradication and tissue preservation are crucial for clinical outcomes.
