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

Author:

Vieira Melo Ana Karoline1ORCID,da Nóbrega Alves Danielle2ORCID,Queiroga Gomes da Costa Palloma Christine1ORCID,Pereira Lopes Susiany3ORCID,Pergentino de Sousa Damião3ORCID,Queiroga Sarmento Guerra Felipe3ORCID,Vieira Sobral Marianna3ORCID,Gomes Moura Ana Paula3,Scotti Luciana3ORCID,Dias de Castro Ricardo3ORCID

Affiliation:

1. Department of Clinical and Social Dentistry Health Sciences Center Federal University of Paraiba Campus I 58051-900 João Pessoa PB Brazil

2. 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

3. Department of Pharmaceutical Sciences Health Sciences Center Federal University of Paraiba Campus I 58051-900 João Pessoa PB Brazil

Abstract

AbstractFungal 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.

Publisher

Wiley

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