Antifungal activity of styrylbenzene compounds against Candida tropicalis

Abstract

Styrylbenzene compounds have been extensively study because its optical properties but their potential biological properties are still undiscovered. The rigid structure of these types of compounds allows to place the therapeutic functionally in specific position, distance and angles and it helps to establish a structure-activity relationship. The synthesis of these structures is based on the Horner-Wadsworth-Emmons (HWE) reaction for the formation of the doubles bonds. This procedure shows few advantages compare with other to generate double bonds. The trans stereochemistry of the double bonds located at the core was preserved throughout the synthetic methodology. This is acritical issue because for establish a structure-activity relationship it is important that comparison among molecules are made with perfectly well known structures, included stereochemistry. On the other hand, the HWE reaction provides a methodology with an easy workup and free of catalyst that typically raise the price of the production and may interfere in the biological properties. The aim of this work was to determine the effect of styrylbezene compounds against Candida tropicalis NCPF 3111.The antifungal activity of four compounds obtained (AFL 8.3, AFL 10.1, AFL 5.1 and AFL 14) was tested against C. tropicalis NCPF 3111 by the determination of minimum inhibitory concentration (MIC)and minimum fungicidal concentration (MFC). The MIC of the four compounds was determinedaccording to the M27-A3 broth microdilution reference procedure of Clinical and Laboratory Standards Institute (CLSI, 2008), at a final inoculum of 1-5 × 103 CFU/mL, RPMI media. Serial dilutions of the compounds, ranging from 0.033 to 512 mg/mL, were carried out in a microdilution plate (96 wells) containing 100 mL of RPMI. The inoculum was then added to each well. The microplates were incubated at 37 °C for 48 h. MIC was defined as the lowest concentration which resulted in inhibitionof visual growth. Minimal fungicidal concentrations were determined by subculturing 100 mL of the culture from each negative well and from the positive control on sabouraud dextrose agar. All these analyses were performed in triplicate. Amphotericin B was used as control, ranging from 0.033 to 16mg/mL. The four compounds evaluated show a greater antifungal activity against C. tropicalis NCPF3111. The values obtained for MIC and MFC were 8 μg/mL for AFL 8.3, 32 and 64 μg/mL for AFL 5.1,64 and 128 μg/mL for AFL 10.1, 16 μg/mL for AFL 14 and 0.25 for amphotericin B. The data obtained revealed a fungicidal activity against yeasts cells of the C. tropicalis, and open new perspectives for future research in continuation to this study, where information such as determination of the site and mechanism of action of the styrylbezene compounds could contribute to an alternative therapy against these organisms.