Synthesis and Study of Antifungal Properties of New Cationic Beta-Glucan Derivatives

Abstract

The interaction of positively charged polymers (polycations) with a biological membrane is considered to be the cause of the frequently observed toxicity of these macromolecules. If it is possible to obtain polymers with a predominantly negative effect on bacterial and fungal cells, such systems would have great potential in the treatment of infectious diseases, especially now when reports indicate the growing risk of fungal co-infections in COVID-19 patients. We describe in this article cationic derivatives of natural beta-glucan polymers obtained by reacting the polysaccharide isolated from Saccharomyces boulardii (SB) and Cetraria islandica (CI) with glycidyl trimethyl ammonium chloride (GTMAC). Two synthesis strategies were applied to optimize the product yield. Fungal diseases particularly affect low-income countries, hence the emphasis on the simplicity of the synthesis of such drugs so they can be produced without outside help. The three structures obtained showed selective anti-mycotic properties (against, i.e., Scopulariopsis brevicaulis, Aspergillus brasiliensis, and Fusarium solani), and their toxicity established using fibroblast 3T3-L1 cell line was negligible in a wide range of concentrations. For one of the polymers (SB derivative), using in vivo model of Aspergillus brasiliensis infection in Galleria mellonella insect model, we confirmed the promising results obtained in the preliminary study.

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

“…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.…”

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

“…There are reports in the literature that go so far as to postulate that the membrane is partly responsible for drug resistance and should therefore be the primary target for new antifungal drugs. 15 The use of positively charged polymers in antifungal applications has been proposed postulatively in mainly agricultural applications 16 and also to a small extent for medical use 17 without clearly indicating a mechanism of action. Their biocidal use against bacteria 18 and partly against higher cells 19 has been reported in the literature, while the mechanisms responsible for these phenomena are also not clearly explained.…”

Antifungal and Aflatoxin-Reducing Activity of β-Glucan Isolated from Pichia norvegensis Grown on Tofu Wastewater

“…Meanwhile Narusaka et al [12] stated that yeast cell walls extracted from S. pastorianus containing ±40% mannoprotein, 60% β-glucan, and 1.3% chitin could inhibit the growth of the fungus Colletotrichum higginsianum by activating resistance to fungi through the Salicylic Acid (SA)-dependent pathway. β-glucan has been found to have a role in decontaminating toxin that remain in the environment including in water, with the advantages that the toxicity is biologically reduced, saving mammalian cells [21,22]. Meanwhile, β-glucan and its cationic derivatives show decontamination effects by means of their polycation structure, which easily react with the fungi's biological membrane, and show antifungal activities [22].…”

“…β-glucan has been found to have a role in decontaminating toxin that remain in the environment including in water, with the advantages that the toxicity is biologically reduced, saving mammalian cells [21,22]. Meanwhile, β-glucan and its cationic derivatives show decontamination effects by means of their polycation structure, which easily react with the fungi's biological membrane, and show antifungal activities [22].…”