Isoeugenol and Hybrid Acetamides against Candida albicans Isolated from the Oral Cavity.

Daianne Medeiros,Helivaldo Souza,Gracielle Silva,José Barbosa-Filho,Jeane Jardim,José Oliveira-Júnior,Luciana Scotti,Laísa Cordeiro,Petrônio Athayde-Filho,Jefferson Nóbrega,Edeltrudes Lima

doi:10.3390/ph13100291

Abstract

Isougenol is a phytoconstituent found in several essential oils. Since many natural products are potent antimicrobials, the synthesis of hybrid molecules—combining the chemical skeleton of the phytochemical with synthetic groups—can generate substances with enhanced biological activity. Based on this, the objective of this study was to evaluate the antifungal activity of isoeugenol and hybrid acetamides against Candida albicans isolated from the oral cavity. The methodologies used were the determination of minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), action on fungal micromorphology, interaction test with nystatin by the checkerboard method and molecular docking study with important enzymes in the maintenance of fungal viability. The synthetic molecules did not demonstrate significant antifungal activity in vitro. The isoeugenol MIC and MFC varied between 128 and 256 µg/mL, being the phytoconstituent able to interfere in the formation of blastoconid and chlamydoconid structures, important in the pathogenic process of the species. The molecular docking study revealed that isoeugenol is a potential inhibitor of the enzymes 14-α-demethylase and delta-14-sterol reductase, interfering in the fungal cell membrane biosynthesis. Thus, this research provides clearer expectations for future pharmacological studies with isoeugenol and derived molecules, aiming at its therapeutic application against infections caused by Candida spp.

Highlights

Candidiasis is an infectious process of clinical importance caused by dimorphic, commensal, opportunistic fungi, belonging to the genus Candida [1]
The data obtained in this study demonstrated that the interaction of isoeugenol with nystatin was indifferent, with index values fractional inhibitory concentration (FIC) = 3.09 and FIC = 2.10, for C. albicans LM-4b and C. albicans American Type Culture Collection (ATCC)-76485, respectively (Table 3)
The results found by Peixoto et al [19] corroborate those observed in this study, in which the value of Minimum Fungicidal Concentration (MFC)/minimum inhibitory concentration (MIC) of the Laurus nobilis essential oil against C. albicans coming from the oral cavity was

Summary

Introduction

Candidiasis is an infectious process of clinical importance caused by dimorphic, commensal, opportunistic fungi, belonging to the genus Candida [1]. It is an infection of considerable public relevance, since yeasts of this genus are responsible for about 80% of hospital fungal infections [2], representing the fourth most common nosocomial pathogen in systemic infections [3], with morbidity and mortality rates between 30–50% [4]. The genus Candida comprises of about 150–200 described species, only fifteen can be pathogenic to humans, with C. albicans, C. glabrata, C. parapsilosis, C. tropicalis and C. krusei being the most prevalent in different types of candidiasis [5,6,7]. Several predisposing factors are associated with a high prevalence of oral candidiasis, including nighttime use of dental prostheses, decreased salivary pH, dry mouth, prolonged use of antibiotic therapy and immunosuppressive drugs, nutritional deficiency, endocrine disorders and increased life expectancy of the population [6,11,12]

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