Eradication of Candida albicans Biofilm Viability: In Vitro Combination Therapy of Cationic Carbosilane Dendrons Derived from 4-Phenylbutyric Acid with AgNO3 and EDTA

Abstract

Candida albicans is a human pathogen of significant clinical relevance. This pathogen is resistant to different drugs, and most clinical antifungals are not effective against the prevention and treatment of C. albicans infections. As with other microorganisms, it can produce biofilms that serve as a barrier against antifungal agents and other substances, contributing to infection in humans and environmental tolerance of this microorganism. Thus, resistances and biofilm formation make treatment difficult. In addition, the complete eradication of biofilms in implants, catheters and other medical devices, is challenging and necessary to prevent relapses of candidemia. Therefore, it is a priority to find new molecules or combinations of compounds with anti-Candida biofilm activity. Due to the difficulty of treating and removing biofilms, the aim of this study was to evaluate the in vitro ability of different generation of cationic carbosilane dendrons derived from 4-phenylbutyric acid, ArCO2Gn(SNMe3I)m, to eradicate C. albicans biofilms. Here, we assessed the antifungal activity of the second generation dendron ArCO2G2(SNMe3I)4 against C. albicans cells and established biofilms since it managed to seriously damage the membrane. In addition, the combinations of the second generation dendron with AgNO3 or EDTA eradicated the viability of biofilm cells. Alterations were observed by scanning electron microscopy and cytotoxicity was assessed on HeLa cells. Our data suggest that the dendritic compound ArCO2G2(SNMe3I)4 could represent an alternative to control the infections caused by this pathogen.

Amoebicidal activity of cationic carbosilane dendrons derived with 4-phenylbutyric acid against Acanthamoeba griffini and Acanthamoeba polyphaga trophozoites and cysts

“…The cytotoxicity of treatment combinations with amoebicidal and amoebostatic activity was evaluated in HeLa cells. Individual evaluation of ArCO 2 G 2 (SNMe 3 I) 4 ( 2 ) and CLX cytotoxicity in HeLa cells performed previously showed that ArCO 2 G 2 (SNMe 3 I) 4 ( 2 ) demonstrated low cytotoxicity in the range of 4–8 mg/L, according to the aforementioned criteria, even after 48 h of exposure 23 . However, CLX exhibited high cytotoxicity at similar concentrations after only 24 h.…”

“…However, the primary outcome was an additive effect, once again (Tables 6 and 7). www.nature.com/scientificreports/ icity in the range of 4-8 mg/L, according to the aforementioned criteria, even after 48 h of exposure 23 . However, CLX exhibited high cytotoxicity at similar concentrations after only 24 h. Effective amoebicidal combinations against trophozoites of both strains showed some cytotoxicity.…”

Special Issue: Alternative Therapeutic Approaches of Candida Infections

“…They observed a remarkable antifungal effect exerted by this complex against planktonic and sessile Candida cells, supporting the usage of this compound for the treatment of oral fungal infections [10]. Gómez-Casanova et al (2021) evaluated the in vitro effect of the combination of cationic carbosilane dendrons derived from 4-phenylbutyric acid in the presence of AgNO 3 and EDTA [11]. They found that the second generation dendron with AgNO 3 or EDTA can decrease the viability of the biofilms formed by C. albicans [11].…”

“…Gómez-Casanova et al (2021) evaluated the in vitro effect of the combination of cationic carbosilane dendrons derived from 4-phenylbutyric acid in the presence of AgNO 3 and EDTA [11]. They found that the second generation dendron with AgNO 3 or EDTA can decrease the viability of the biofilms formed by C. albicans [11]. A comprehensive study performed by Jakab et al (2021) showed the negative effect of protein phosphatase Z1 deletion on oxidative stress tolerance, helping the development of further, novel antifungal drugs [12].…”

Novel Treatment Approach against Candida spp.: Evaluation of Antifungal and Antibiofilm In Vitro Activity of Dendritic Molecules

“…Therefore, we would be missing tremendously relevant information and we would be giving inaccurate information. However, studies carried out with the resazurin method have shown good efficacy and reliable and complete results [19][20][21][22]. Resazurin does not require additives or dissolve salts with DMSO, as is the case with the dyes mentioned above (Figure 1).…”