Ação antifúngica de derivados amino álcoois e diaminas frente aos principais causadores de onicomicoses

Abstract

Onychomycosis is a fungal infection characterized clinically by morphological changes in the nail tissue provided mainly by dermatophyte filamentous fungi, the main etiological agent. This mycosis is considered a public health problem and presents numerous factors that may favor its beginning. Its treatment is considered a great challenge for medicine, once it is prolonged, it presents reduced efficacy and frequent recurrences, besides causing adverse effects to the patients. In view of the above, there is a need to obtain new pharmacologically active compounds for this purpose. In this context, the synthesis of organic compounds and the investigation of the antifungal potential may boost the elucidation of new antifungal agents. Therefore, the objective of this work was to evaluate the antifungal activity in vitro of diamines and amino alcohols against the main fungi causing onychomycosis. For this, antifungal analysis was carried out to establish the minimum inhibitory concentrations (MIC) and minimum fungicide (CFM) against Trichophyton mentagrophytes ATCC 11481, T. rubrum CCT 5507 URM 1666, Epidermophyton floccosum CCF-IOF-3757, Candida albicans ATCC 10231 and a clinical isolate of C. albicans. A scanning electron microscopy (SEM) along with the evaluation of fungal virulence factors (phospholipase and melanin). Finally, the in vitro cytotoxicity of amino alcohols against fibroblast cells (L929) and keratinocytes (HaCaT) was further investigated. From a group of fifty synthesized molecules, three amino acohols with 10, 12 and 14 C aliphatic chain were selected which were fungicidal against the five fungal strains evaluated with MIC values ranging from 0.46-1,000 μg/ mL and CFM between 7.81-1,000 μg/ mL. Among them, the amino alcohol with 14 C was featured. Using the electromicrographs, it was possible to show morphological changes in the fungal structures of the five species submitted to the action of the selected amino alcohols, which demonstrates their action on the evaluated fungi. The compounds provided interference in phospholipase excretion, however, did not interfere with melanin production. Amino alcohols revealed relative toxicity to L929 and HaCaT cells. Thus, the findings contribute to the structural modification of the molecules analyzed and / or synthesis of new compounds more effective and less toxic for the treatment of mycosis.