Clioquinol and 8-hydroxyquinoline-5-sulfonamide derivatives damage the cell wall of Pythium insidiosum.

AIMS: To evaluate the antimicrobial activity and to determine the pharmacodynamic characteristics of three 8-hydroxyquinoline derivatives (8-HQs) against Pythium insidiosum, the causative agent of pythiosis. METHODS AND RESULTS: Antimicrobial activity was tested by broth microdilution and MTT assays. The antimicrobial mode of action was investigated using sorbitol protection assay, ergosterol binding assay, and scanning electron microscopy. Clioquinol, PH151, and PH153 were active against all isolates, with MIC values ranging from 0.25 to 2 µg ml-1. They also showed a time- and dose-dependent antimicrobial effect, damaging the P. insidiosum cell wall. CONCLUSIONS: Together, these results reinforce the potential of 8-HQs for developing new drugs to treat pythiosis.

8-hydroxyquinoline and quinazoline derivatives as potential new alternatives to combat Candida spp. biofilm.

Often associated to the colonization by Candida spp. biofilm, the catheter-related infections are a serious health problem since the absence of a specific therapy. Hence, the main objective of this work was to evaluate the activity of 8-hydroxyquinoline and quinazoline derivatives on Candida spp. biofilms. A quinazoline derivative (PH100) and an 8-hydroxyquinoline derivative (PH157) were tested against nine strains of C. albicans, C. tropicalis and C. parapsilosis, and their biofilms in polystyrene microtitre plates and on polyurethane central venous catheter. The PH157 compound was incorporated into a film-forming system-type formulation and its capacity to inhibit biofilm formation on catheters was evaluated. The compounds were active against planktonic and sessile cells, as well as against the tested biofilms. PH157 compound performed better than the PH100 compound. The formulation containing PH157 presented results very similar to those of the compound in solution, which indicates that its activity was preserved. Both compounds showed activity against Candida spp. strains and their biofilm, with better PH157 activity. The formulation preserved the action of the PH157 compound, in addition, it facilitates its application on the catheter. The structural modifications that these compounds allow can generate compounds that are even more active, both against planktonic cells and biofilms.

The efficacy of 8-hydroxyquinoline derivatives in controlling the fungus Ilyonectria liriodendri, the causative agent of black foot disease in grapevines.

AIM: The purpose of this study was to evaluate the in vitro and in vivo efficiency of derivatives of 8-Hydroxyquinoline (8HQ) in controlling the fungus Ilyonectria liriodendri. METHODS AND RESULTS: The in vitro tests consisted of assessing its susceptibility to the minimal inhibitory concentration (MIC) and the inhibition of mycelial growth. While the in vivo tests consisted of applying and assessing the most effective products for the protection of wounds, in both preventive + curative and curative forms. The MIC values for PH 151 (6·25 µg ml-1 ) showed better results when compared to the fungicides tebuconazole (>50 µg ml-1 ) and mancozeb (12·5 µg ml-1 for strain 176 and 25 µg ml-1 for strain 1117). PH 151 significantly inhibited mycelial growth, while mancozeb did not differ from the control. In in vivo tests, PH 151 again demonstrated excellent results in vitro, especially when applied preventively. CONCLUSIONS: The derivative of 8HQ PH 151 was effective in controlling the fungus I. liriodendri in vitro and proved to be a promising option for protecting wounds. SIGNIFICANCE AND IMPACT OF THE STUDY: This study points to the prospect of an effective and safe preventive antifungal product, which would enable the use of pesticides in vine culture to be reduced.

Antifungal activity and toxicological parameters of 8-hydroxyquinoline-5-sulfonamides using alternative animal models.

AIM: The purpose of this study was to evaluate the antifungal activity and toxicological parameters of 8-hydroxyquinoline derivatives PH151 and PH153 using alternative animal models, to understand their behaviour when subjected to in vivo experiments. METHODS AND RESULTS: We used Toll-deficient Drosophila melanogaster to test the protective effect of compounds against Candida albicans infection. Toxicological parameters were investigated in chicken and zebrafish embryos. PH151 and PH153 showed low toxicity and the treated flies with these compounds had a significantly higher survival rate than untreated flies after 7 days of infection. The compounds did not cause interruption of chicken embryogenesis. Zebrafish embryos exposed to compounds showed dose-dependent toxicity. CONCLUSIONS: The data supported the potential of PH151 and PH153 for the treatment of systemic candidiasis and demonstrated to be appropriate drug candidates for further studies using mammalian models. SIGNIFICANCE AND IMPACT OF THE STUDY: The increased incidence of Candida infections resistant to antifungals currently available requires acceleration of the discovery of new agents with properties of inhibiting this fungal pathogen. In this study, we have described the antifungal potential and toxicity of two 8-hydroxyquinoline derivatives using in vivo alternative models, and the results confirm their potential to be developed as new drug candidates.

8-Hydroxyquinoline-5-sulfonamides are promising antifungal candidates for the topical treatment of dermatomycosis.

AIM: The purpose of this study was to uncover insights into the mechanism of action of the 8-hydroxyquinoline derivatives PH151 and PH153. In addition, with the future perspective of developing a topical drug for the treatment of candidiasis and dermatophytosis, the antifungal activity of a nanoemulsion formulation containing the most active compound (PH151) is also presented here. METHODS AND RESULTS: Sorbitol protection assay and scanning electron microscopy indicate that the 8-hydroxyquinoline derivatives act on the cell wall of Candida sp. and dermatophytes and they inhibit the pseudohyphae formation of C. albicans. These findings demonstrate a strong effect of these compounds on C. albicans morphogenesis, which can be considered a potential mode of action for this molecule. Besides, the nanoemulsion formulation MIC values ranged from 0·5 to 4 µg ml-1 demonstrating the significant antifungal activity when incorporated into a pharmaceutical formulation. CONCLUSIONS: Taken together, the results support the potential of these molecules as promising antifungal candidates for the treatment of candidiasis and dermatophytosis. SIGNIFICANCE AND IMPACT OF THE STUDY: There is an emerging need to fill the pipeline with new antifungal drugs due to the limitations presented by the currently used drugs. In this study, we have described a novel formulation with a 8-hydroxyquinoline-5-sulfonamide derivative which has presented a great potency in providing a finished product. Furthermore, the derivative has shown a selective mechanism of action confirming its potential to be developed into a new drug candidate.

Pythium insidiosum: insights into biofilm formation and antibiofilm activity of antifungal drugs.

In this study, we investigate the ability of Pythium insidiosum to form biofilms across various substrates and the antibiofilm efficacy of 8-hydroxyquinoline derivatives (8-HQs). Biofilms of P. insidiosum were cultured on polystyrene plates, contact lenses, and horsehair. We provide the first evidence of P. insidiosum's biofilm-forming capability, thus considerably expanding our understanding of its transmission and pathogenesis. Our results demonstrate that 8-HQs effectively inhibit biofilm formation and eradicate pre-existing biofilms, underscoring their potential as a novel treatment strategy for pythiosis, a disease currently lacking a gold-standard treatment. This finding has particular relevance for ocular pythiosis associated with contact lens usage and potential infection sources in animals. Our results contribute to the scientific knowledge base and directly impact innovative therapeutic interventions' development.