Preliminary Studies on the Mechanism of Antifungal Activity of New Cationic β-Glucan Derivatives Obtained from Oats and Barley

Abstract

New chemical structures with antifungal properties are highly desirable from the point of view of modern pharmaceutical science, especially due to the increasingly widespread instances of drug resistance in the case of these diseases. One way to solve this problem is to use polymeric drugs, widely described as biocidal, positively charged macromolecules. In this work, we present the synthesis of new cationic β-glucan derivatives that show selective antifungal activity and at the same time low toxicity toward animal and human cells. Two β-glucans isolated from oats and barley and modified using glycidyltrimethylammonium chloride were obtained and evaluated for biocidal properties on the cells of mammals and pathogenic fungi and bacteria. These compounds were found to be nontoxic to fibroblast and bacterial cells but showed selective toxicity to certain species of filamentous fungi (Scopulariopsis brevicaulis) and yeasts (Cryptococcus neoformans). The most important aspect of this work is the attempt to explain the mechanisms of action of these compounds by studying their interaction with biological membranes. This was achieved by examining the interactions with model biological membranes representative of given families of microorganisms using Langmuir monolayers. The data obtained partly show correlations between the results for model systems and biological experiments and allow indicating that the selective antifungal activity of cationic β-glucans is related to their interaction with fungal biological membranes and partly lack of such interaction toward cells of other organisms. In addition, the obtained macromolecules were characterized by spectral methods (Fourier transform infrared (FTIR) and 1 H nuclear magnetic resonance (NMR) spectroscopies) to confirm that the desired structure was obtained, and their degree of modification and molecular weights were determined.

The Use of a Barley-Based Well to Define Cationic Betaglucan to Study Mammalian Cell Toxicity Associated with Interactions with Biological Structures

“…The procedures described in this work for the isolation of betaglucan and purification from cereals are based on earlier descriptions in the literature [ 10 ] where effective isolation of these polysaccharides has been confirmed. The cationization reaction is an expansion of a procedure we also described in an earlier paper [ 21 ].…”

“…Betaglucan was isolated from whole-grain barley flour according to the recipe described earlier [ 10 , 28 ]. Briefly, the procedure went as follows.…”

“…Cationization of the isolated crude betaglucan was carried out as described in our earlier publication [ 10 ]. Briefly, for BBGGTMAC1 and BBGGTMAC2 polymers, crude betaglucan was suspended in 50 cm 3 of water, followed by the addition of 200 mg of NaOH and GTMAC (exact amounts according to the Table 1 ).…”

“…Another noteworthy biological property of polycations is their biocidal properties, in particular antibacterials [ 9 ]. Recent years have also brought reports of antifungal properties [ 10 ] confirmed on in vivo infection models [ 11 ]. In the era of the growing problem with drug resistance of pathogenic bacteria and fungi [ 12 ], polycations could potentially be the foundation for a new family of antibiotics.…”

Oat Peptides Alleviate Dextran Sulfate Sodium Salt-Induced Colitis by Maintaining the Intestinal Barrier and Modulating the Keap1-Nrf2 Axis

“…For example, oats have antioxidant activities [8,9], which may be related to the phenolic substances present [10][11][12][13]. The βglucan in oats has antifungal effects [14] and can alleviate dextran sulfate sodium salt (DSS)-induced enteritis [15], an effect that may be related to its modulatory effect on intestinal microbial metabolism [16]. In addition, the soluble fiber in oats can alleviate trinitrobenzene sulfonic acid (TNBS)-induced enteritis by inducing regulatory T-cell (Treg) differentiation [17].…”