Atividade antifúngica de novas naftoquinonas semissintéticas frente a fungos oportunistas e dermatófitos e ensaios preliminares de seus mecanismos de ação

Abstract

Introduction: The increase in fungal infections, adverse effects and resistance to antifungal agents currently used, stimulate new studies in search of better antifungal. In this context, the naphthoquinones are widely studied for possessing various biological activities, among them antifungal. The aim of this study was to evaluate the antifungal activity of new naphthoquinones semissintéticas against opportunistic fungi / dermatophytes and to evaluate the interference of a naphthoquinone selected in cell wall formation, membrane ergosterol and cell membrane strain of Candida albicans (ATCC 36232). Methods: The antifungal activity of four new naphthoquinones semi synthetic was evaluated against 89 cultures of microorganisms belonging to the collection of the National Institute for Amazonian Research (INPA), including opportunistic yeast, agents of dermatophytosis and opportunistic filamentous fungi. The test for determining the minimum inhibitory concentration (MIC) was performed as described by the CLSI (Clinical and Laboratory Standards Institute) documents M27 - A2 and M38-A/CLSI, 2002. The substance showed better activity was assessed as the action in the cell wall (test sorbitol) and interference in the membrane -associated interaction with ergosterol , the osmotic balance ( K + efflux ) and an essay by leakage of substances that absorb at 260 nm. Results: All new naphthoquinones tested exhibited antifungal activity, and the IVS320 (1H - cyclopenta [ b ] naphtho [2,3 - d] furan- 5 , 10 (3Ah , 10BH) - dione) showed the lowest MICs front species tested. The MIC IV320 was particularly low for dermatophytes , with MIC averages ranging from 5-28 mg / mL and against isolates of the genus Cryptococcus spp . Mean MIC ranged from 5.3 mg / mL. So it was subjected to preliminary tests of mechanism of action. In these trials , the IVS320 caused no change in the fungal cell wall , but caused problems in cell membrane permeability ( efflux of K + and leakage of substances that absorb 260nm ) unrelated to the connection with the ergosterol membrane .