Vanessa Zafaneli Bergamo

Imidazolium salts as antifungal agents: strong antibiofilm activity against multidrug-resistant Candida tropicalis isolates

The in vitro activity of the imidazolium salt C16MImCl against planktonic and biofilm cells of multidrug‐resistant isolates of Candida tropicalis was evaluated, both in solution and applied on a commercial catheter surface. This was determined by inhibition and susceptibility assays of biofilm and planktonic cells. In both cases, C16MImCl prevented in vitro biofilm formation of C. tropicalis strains, including multidrug‐resistant ones. Outstanding performances were observed, even at extremely low concentrations. Furthermore, this is the first report of the antifungal lock property of C16MImCl, using a tracheal catheter as the test specimen to mimic a clinical in vivo condition. As such, C16MImCl has been identified as a promising antimicotic pharmaceutical candidate for the treatment of candidiasis infections.

Imidazolium Salts as Antifungal Agents: Activity Against Emerging Yeast Pathogens, Without Human Leukocyte Toxicity

This study demonstrates the excellent in vitro antifungal activity profile of imidazolium ionic liquids (ILs) against species of opportunistic human mycoses. Several ILs were identified as more effective and less harmful than commercially available antifungal medications. Frequently, emerging yeast pathogens are resistant against commercial antifungal agents and, as a consequence, this class of imidazolium ILs represents a promising breakthrough in their treatment.

Imidazolium salts with antifungal potential against multidrug-resistant dermatophytes.

To investigate the antidermatophytic action of a complementary set imidazolium salts (IMS), determining structure‐activity relationships and characterizing the IMS toxicological profiles.

Evaluation of 8-Hydroxyquinoline Derivatives as Hits for Antifungal Drug Design

Abstract Clioquinol is an 8‐hydroxyquinoline derivative that was widely used from the 1950s to 1970s as an oral antiparasitic agent. In 1970, the oral forms were withdrawn from the market due to reports of toxicity, but topical formulations for antifungal treatment remained available. Thus, the purpose of this study was to evaluate the toxicity, anti‐Candida and antidermatophyte activity and to determine pharmacodynamic characteristics of clioquinol and other 8‐hydroxyquinoline derivatives (8‐hydroxy‐5‐quinolinesulfonic acid and 8‐hydroxy‐7‐iodo‐5‐quinolinesulfonic acid). Antifungal activity was tested by broth microdilution and the fungicidal or fungistatic effect was checked by a time‐kill assay. Permeation and histopathological evaluation were performed in Franz diffusion cells with ear skin of pigs and examined under light microscopy. An HET‐CAM test was used to determine the potential irritancy. The three compounds were active against all isolates showing anti‐Candida and antidermatophyte activity, with MIC ranges of 0.031‐2 &mgr;g/ml, 1‐512 &mgr;g/ml, and 2‐1024 &mgr;g/ml for clioquinol, 8‐hydroxy‐5‐quinolinesulfonic acid, and 8‐hydroxy‐7‐iodo‐5‐quinolinesulfonic acid, respectively. All compounds showed fungistatic effect for Candida, 8‐hydroxy‐5‐quinolinesulfonic acid, and 8‐hydroxy‐7‐iodo‐5‐quinolinesulfonic acid showed a fungicidal effect for M. canis and T. mentagrophytes, and clioquinol showed a fungicidal effect only for T. mentagrophytes. Furthermore, they presented a fungicidal effect depending on the time and concentration. The absence of lesions was observed in histopathological evaluation and no compound was irritating. Moreover, clioquinol and 8‐hydroxy‐5‐quinolinesulfonic acid accumulated in the epithelial tissue, and 8‐hydroxy‐7‐iodo‐5‐quinolinesulfonic acid had a high degree of permeation. In conclusion, 8‐hydroxyquinoline derivatives showed antifungal activity and 8‐hydroxy‐5‐quinolinesulfonic acid demonstrated the potential for antifungal drug design.

Biocompatible succinic acid-based polyesters for potential biomedical applications: fungal biofilm inhibition and mesenchymal stem cell growth

Herein, we present the intrinsic property of well-known polyesters [poly(alkene succinates)], as Candida albicans and Candida tropicalis biofilm inhibitors with potential to substantially reduce the incidence of device-associated infections in, e.g., indwelling catheters and sutures. These new biopolymer applications, either for manufacturing or coating medical devices, present innovative features such as: simple and cheap preparation, easy scaling-up, good mechanical and thermal resistance properties, and antibiofilm ability without any specific surface functionalization or antimicrobial agent encapsulation. Furthermore, the polyesters are shown to be highly biocompatible, promote human mesenchymal stem cell (hMSC) attachment and proliferation, inducing morphological changes, which are dependent on the polymer structural characteristics, making them promising candidates for materials in specialized medical devices and in the tissue engineering field.

Clioquinol is a promising preventive morphological switching compound in the treatment of Candida infections linked to the use of intrauterine devices

Purpose. Candida biofilm infections are frequently linked to the use of biomaterials and are of clinical significance because they are commonly resistant to antifungals. Clioquinol is an antiseptic drug and is effective against multidrug‐resistant Candida. We investigated the effect of clioquinol and two other 8‐hydroxyquinoline derivatives on Candida biofilm. Methodology. The ability to inhibit biofilm formation, inhibit preformed biofilm and remove established biofilms was evaluated using in vitro assays on microtitre plates. The action of clioquinol on biofilm in intrauterine devices (IUDs) was also investigated, describing the first protocol to quantify the inhibitory action of compounds on biofilms formed on IUDs. Results. Clioquinol was found to be the most effective 8‐hydroxyquinoline derivative among those tested. It prevented more than 90 % of biofilm formation, which can be attributed to blockade of hyphal development. Clioquinol also reduced the metabolic activity of sessile Candida but the susceptibility was lower compared to planktonic cells (0.031‐0.5 &mgr;g ml‐1 required to inhibit 50 % planktonic cells and 4‐16 &mgr;g ml‐1 to inhibit 50 % preformed biofilms). On the other hand, almost complete removal of biofilms was not achieved for the majority of the isolates. Candida spp. also showed the ability to form biofilm on copper IUD; clioquinol eradicated 80‐100 % of these biofilms. Conclusion. Our results indicate a potential application in terms of biomaterials for 8‐hydroxyquinoline derivatives. Clioquinol could be used as a coating to prevent morphological switching and thus prevent biofilm formation. Furthermore, clioquinol may have future applications in the treatment of Candida infections linked to the use of IUDs.

Novas tendências de combate ao biofilme de Candida em próteses dentárias

Apesar de a especie Candida albicans ser efetivamente o microrganismo mais frequentemente associado a estomatite protetica, as especies de Candida nao albicans ja foram isoladas nas superficies de dentaduras e da mucosa oral de individuos com essa lesao eritematosa. A virulencia das especies de Candida e a capacidade de adesao a polimeros acrilicos sao condicoes previas para a colonizacao e o desenvolvimento de biofilmes em superficies de dentaduras. Estudos recentes focam na tentativa de modificacao das resinas acrilicas para diminuir a adesao de cepas patogenicas e formadoras de biofilme do genero Candida spp. Dentro desse aspecto, esta revisao sistematiza o atual panorama epidemiologico da estomatite protetica associada ao uso de proteses dentarias, bem como as atuais e novas opcoes de combate ao biofilme fungico especializado na adesao desse tipo de biomaterial. Palavras-chave: Candida spp.; biofilme; estomatite protetica; resina acrilica; tratamento

Assessing an imidazolium salt's performance as antifungal agent on a mouthwash formulation.

This study demonstrates the development of a mouthwash formulation containing the imidazolium salt (IMS) 1‐n‐hexadecyl‐3‐methylimidazolium chloride (C16MImCl), considering its stability and efficacy against Candida sp. Biofilm formation.