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

Autor: Vieira Melo AK; Department of Clinical and Social Dentistry, Health Sciences Center, Federal University of Paraiba, Campus I, 58051-900, João Pessoa, PB, Brazil., da Nóbrega Alves D; Department of Clinical and Social Dentistry, Health Sciences Center, Federal University of Paraiba, Campus I, 58051-900, João Pessoa, PB, Brazil, Lauro Wanderley University Hospital, 58050-585, João Pessoa, PB, Brazil., Queiroga Gomes da Costa PC; Department of Clinical and Social Dentistry, Health Sciences Center, Federal University of Paraiba, Campus I, 58051-900, João Pessoa, PB, Brazil., Pereira Lopes S; Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Paraiba, Campus I, 58051-900, João Pessoa, PB, Brazil., Pergentino de Sousa D; Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Paraiba, Campus I, 58051-900, João Pessoa, PB, Brazil., Queiroga Sarmento Guerra F; Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Paraiba, Campus I, 58051-900, João Pessoa, PB, Brazil., Vieira Sobral M; Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Paraiba, Campus I, 58051-900, João Pessoa, PB, Brazil., Gomes Moura AP; Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Paraiba, Campus I, 58051-900, João Pessoa, PB, Brazil., Scotti L; Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Paraiba, Campus I, 58051-900, João Pessoa, PB, Brazil., Dias de Castro R; Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Paraiba, Campus I, 58051-900, João Pessoa, PB, Brazil.
Jazyk: angličtina
Zdroj: Chemistry & biodiversity [Chem Biodivers] 2024 Jul; Vol. 21 (7), pp. e202400330. Date of Electronic Publication: 2024 Jun 14.
DOI: 10.1002/cbdv.202400330
Abstrakt: 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.
(© 2024 Wiley-VHCA AG, Zurich, Switzerland.)
Databáze: MEDLINE
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