Antifungal Activity and Potential Mechanism of Panobinostat in Combination With Fluconazole Against Candida albicans

Su, Shan; Shi, Xiaohong; Xu, Wei; Li, Yiman; Chen, Xueqi; Song, Jia; Sun, Shujuan

doi:10.3389/fmicb.2020.01584

Cited by 11 publications

(3 citation statements)

References 54 publications

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“…Maximum values of six and eight for the combination of 3′-HC + 2-HC and 2-HC + FCZ, as well as isolated substances and for the lipid carriers LC (1) and LC (2), were observed, demonstrating that these combinations did not show toxicity and that they may be promising in the treatment of VVC. Similar studies have demonstrated the effectiveness of the agreement model in the evaluation of drugs combined with fluconazole (FCZ) against C. albicans [82].…”

Section: Discussionmentioning

confidence: 68%

Bioprospecting, Synergistic Antifungal and Toxicological Aspects of the Hydroxychalcones and Their Association with Azole Derivates against Candida spp. for Treating Vulvovaginal Candidiasis

Fernandes,

Ogasawara,

Medina-Alarcón

et al. 2024

Pharmaceutics

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Vulvovaginal candidiasis (VVC) remains a prevalent fungal disease, characterized by challenges, such as increased fungal resistance, side effects of current treatments, and the rising prevalence of non-albicans Candida spp. naturally more resistant. This study aimed to propose a novel therapeutic approach by investigating the antifungal properties and toxicity of 2-hydroxychalcone (2-HC) and 3′-hydroxychalcone (3′-HC), both alone and in combination with fluconazole (FCZ) and clotrimazole (CTZ). A lipid carrier (LC) was also developed to deliver these molecules. The study evaluated in vitro anti-Candida activity against five Candida species and assessed cytotoxicity in the C33-A cell line. The safety and therapeutic efficacy of in vivo were tested using an alternative animal model, Galleria mellonella. The results showed antifungal activity of 2-HC and 3′-HC, ranging from 7.8 to 31.2 as fungistatic and 15.6 to 125.0 mg/L as fungicide effect, with cell viability above 80% from a concentration of 9.3 mg/L (2-HC). Synergistic and partially synergistic interactions of these chalcones with FCZ and CTZ demonstrated significant improvement in antifungal activity, with MIC values ranging from 0.06 to 62.5 mg/L. Some combinations reduced cytotoxicity, achieving 100% cell viability in many interactions. Additionally, two LCs with suitable properties for intravaginal application were developed. These formulations demonstrated promising therapeutic efficacy and low toxicity in Galleria mellonella assays. These results suggest the potential of this approach in developing new therapies for VVC.

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Section: Discussionmentioning

confidence: 68%

Bioprospecting, Synergistic Antifungal and Toxicological Aspects of the Hydroxychalcones and Their Association with Azole Derivates against Candida spp. for Treating Vulvovaginal Candidiasis

Fernandes,

Ogasawara,

Medina-Alarcón

et al. 2024

Pharmaceutics

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“…To assess whether standardization of the G. mellonella rearing process leads to healthier larvae, the survival of standardized reared larvae was compared with that of commercially bred larvae purchased from Kreca Ento‐Feed (Ermelo, The Netherlands). To this end, a survival assay was carried out using two C. albicans reference strains (CBS562 and CBS6431), which were previously shown to be virulent in G. mellonella (Frenkel et al, 2016; Cotter et al, 2000; Romera et al, 2020; Su et al, 2020). In a dose–response assay, a range of inoculum concentrations of both strains was injected to groups of larvae, to determine how many cells are needed to kill at least 50% of the larvae (LD 50 ).…”

Section: Methodsmentioning

confidence: 99%

Standardized methods to rear high‐quality Galleria mellonella larvae for the study of fungal pathogens

Jong

Veldhuizen

Groot

et al. 2022

Entomologia Exp Applicata

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The greater wax moth, Galleria mellonella (L.) (Lepidoptera: Pyralidae), has gathered widespread interest in the biomedical research community as an alternative nonmammalian model to study bacterial and fungal infections in humans. Nevertheless, most laboratories rely on commercial breeding companies that grow these larvae in bulk. Variation in rearing conditions between these companies and shipping of the larvae affects the response of G. mellonella to infection, both decreasing the reproducibility and comparability of infection experiments across laboratories. To unlock the full potential of G. mellonella as an infection model, standardized rearing is essential to produce healthy larvae of uniform quality. To this end, we developed an optimized protocol using a high-nutritional artificial diet and cost-effective housing solutions to ensure optimal conditions during each stage of the G. mellonella life cycle. This resulted in the rapid generation of larvae with a short larval phase, large size, and increased weight compared to other protocols and commercial larvae. A survival analysis comparing the standardized larvae with commercially obtained larvae showed significantly higher survival of standardized reared larvae after infection with Candida albicans (CP Robin) Berkhout (Saccharomycetales), proving the higher quality of standardized reared larvae.

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“…In C. albicans , HDAC is related to fungal pathogenicity and virulence, especially in the aspect of drug resistance. Studies have shown that HDAC inhibitors in combination with azoles against drug-resistant C. albicans showed synergistic effects in vitro , and histone deacetylation modification may be one of the upstream resistant mechanisms of C. albicans ( Su et al, 2020b ). The study of modification in Aspergillus will improve our understanding of the pathogenic fungus Aspergillus and provide a theoretical foundation for the prevention and management of fungi.…”

Section: Histone Deacetylasesmentioning

confidence: 99%

Potential antifungal targets based on histones post-translational modifications against invasive aspergillosis

Song²,

Wang³

et al. 2022

Front. Microbiol.

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As a primary cause of death in patients with hematological malignancies and transplant recipients, invasive aspergillosis (IA) is a condition that warrants attention. IA infections have been increasing, which remains a significant cause of morbidity and mortality in immunocompromised patients. During the past decade, antifungal drug resistance has emerged, which is especially concerning for management given the limited options for treating azole-resistant infections and the possibility of failure of prophylaxis in those high-risk patients. Histone posttranslational modifications (HPTMs), mainly including acetylation, methylation, ubiquitination and phosphorylation, are crucial epigenetic mechanisms regulating various biological events, which could modify the conformation of histone and influence chromatin-associated nuclear processes to regulate development, cellular responsiveness, and biological phenotype without affecting the underlying genetic sequence. In recent years, fungi have become important model organisms for studying epigenetic regulation. HPTMs involves in growth and development, secondary metabolite biosynthesis and virulence in Aspergillus. This review mainly aims at summarizing the acetylation, deacetylation, methylation, demethylation, and sumoylation of histones in IA and connect this knowledge to possible HPTMs-based antifungal drugs. We hope this research could provide a reference for exploring new drug targets and developing low-toxic and high-efficiency antifungal strategies.

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Antifungal Activity and Potential Mechanism of Panobinostat in Combination With Fluconazole Against Candida albicans

Cited by 11 publications

References 54 publications

Bioprospecting, Synergistic Antifungal and Toxicological Aspects of the Hydroxychalcones and Their Association with Azole Derivates against Candida spp. for Treating Vulvovaginal Candidiasis

Bioprospecting, Synergistic Antifungal and Toxicological Aspects of the Hydroxychalcones and Their Association with Azole Derivates against Candida spp. for Treating Vulvovaginal Candidiasis

Standardized methods to rear high‐quality Galleria mellonella larvae for the study of fungal pathogens

Potential antifungal targets based on histones post-translational modifications against invasive aspergillosis

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