In vitro antifungal activity of MMV Pathogen Box® compounds, alone or in combination with antifungal drugs, against mucormycosis agents DOI Creative Commons
Fernando Almeida‐Silva,

Pedro Henrique Tenório-Alvarenga,

Raiane Valle da Costa

et al.

Current Research in Microbial Sciences, Journal Year: 2024, Volume and Issue: 6, P. 100242 - 100242

Published: Jan. 1, 2024

Mucormycosis is a severe fungal infection that demands immediate and decisive intervention upon suspicion. The causative agents of mucormycosis exhibit inherent resistance to echinocandins voriconazole, their in vitro susceptibility terbinafine highly variable species-specific. Considering these factors the limitations currently available antifungal therapies, identification novel antifungals with potent activity against paramount importance. This study aims identify compounds from MMV Pathogen Box® presenting selected evaluate potential synergistic effects when combined drugs. A screening was conducted, isolated or combination sub-inhibitory concentrations amphotericin B, isavuconazole posaconazole, Rhizopus oryzae strain. Hits screenings were further evaluated eight Mucoralean strains for minimal inhibitory fungicidal concentration determinations confirm interactions using checkerboard method. Ultrastructural studies performed scanning electron microscopy. MMV675968 exhibited R. All but one spp. presented MIC ≤ 1 μg/mL, geometric mean 0.78 μg/mL observed across all isolates this compound, which did not change significantly cellular structure fungus. drugs revealed six additional potentially active strain, two them demonstrated proven synergism through assay. first Zigomycetes highlights promising new treatment options future.

Language: Английский

The Significance of Mono‐ and Dual‐Effective Agents in the Development of New Antifungal Strategies DOI Creative Commons

Cengiz Zobi,

Öztekin Algül

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(1)

Published: Jan. 1, 2025

ABSTRACT Invasive fungal infections (IFIs) pose significant challenges in clinical settings, particularly due to their high morbidity and mortality rates. The rising incidence of these infections, coupled with increasing antifungal resistance, underscores the urgent need for novel therapeutic strategies. Current drugs target cell membrane, wall, or intracellular components, but resistance mechanisms such as altered drug‐target interactions, enhanced efflux, adaptive cellular responses have diminished efficacy. Recent research has highlighted potential dual inhibitors that simultaneously multiple pathways enzymes involved growth survival. Combining pharmacophores, lanosterol 14α‐demethylase (CYP51), heat shock protein 90 (HSP90), histone deacetylase (HDAC), squalene epoxidase (SE) inhibitors, led development compounds activity reduced resistance. This dual‐target approach, along chemical scaffolds, not only represents a promising strategy combating is also being utilized anticancer agents. review explores new agents employ mono‐, dual‐, multi‐target strategies combat IFIs. We discuss emerging targets, mechanisms, innovative approaches offer hope managing challenging infections.

Language: Английский

Citations

2
Current strategies in design and synthesis of antifungals hybrid and chimeric diazine derivatives DOI Creative Commons
Dumitrela Diaconu,

Marius Savu,

Catalina Ionica Ciobanu

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 119, P. 118069 - 118069

Published: Jan. 13, 2025

Language: Английский

Citations

1
Essential Oil Components Incorporated Emulsion Hydrogels for Eradicating Dermatophytosis Caused by Pathogenic Fungi Trichophyton mentagrophytes and Microsporum canis DOI
Namitha K. Preman,

Nikhitha Amin,

Sandesh G. Sanjeeva

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(29)

Published: Aug. 13, 2024

Dermatophytosis is a prevalent fungal infection and public health burden, majorly caused by the attack of zoophilic fungi genera Trichophyton Microsporum. Among them, T. mentagrophytes M. canis are dominating pathogens that cause dermatophytosis in humans. Though anti-fungal treatments available, widespread drug resistance minimal efficacy conventional therapies recurring infections. In addition, prolonged medications induce several systemic side effects, including hepatotoxicity leucopenia. The anti-dermatophytic formulation biocompatible essential oil components (EOCs) attractive due to their highly potent action. Herein, two EOCs, Eugenol (EU) Isoeugenol (IU), incorporated emulsion hydrogel (EOCs-EHG) synthesized from hydroxypropylmethyl cellulose poly(ethylene glycol) methyl ether methacrylate. cytocompatibility hydrogels confirmed treating them with fibroblast keratinocyte cell lines. EOCs-EHG demonstrated pH temperature-responsive sustained release entrapped EOCs inhibited spore germination. biofilms eradicated at inhibitory concentration 2 µg mL

Language: Английский

Citations

3
The Contribution of Human Antimicrobial Peptides to Fungi DOI Open Access

Qiaoxi Zhang,

Ki Ryung Choi,

Xiaoyue Wang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2494 - 2494

Published: March 11, 2025

Various species of fungi can be detected in the environment and within human body, many which may become pathogenic under specific conditions, leading to various forms fungal infections. Antimicrobial peptides (AMPs) are evolutionarily ancient components immune response that quickly induced infections with pathogens almost all tissues. There is a wide range AMP classes humans, exhibit broad-spectrum antimicrobial function. This review provides comprehensive overview mechanisms action AMPs, their distribution antifungal activity against both common rare clinical pathogens. It also discusses current research status promising novel strategies, highlighting challenges must overcome development these therapies. The hope peptides, as class agents, will soon progress through large-scale trials implemented practice, offering new treatment options for patients suffering from

Language: Английский

Citations

0
Hybrid Bis-(Imidazole/Benzimidazole)-Pyridine Derivatives with Antifungal Activity of Potential Interest in Medicine and Agriculture via Improved Efficiency Methods DOI Creative Commons
Tiberius Balaeş, Violeta Mangalagiu, Vasilichia Antoci

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 495 - 495

Published: March 28, 2025

Background/Objectives: Nowadays fungal infections are rising serious threats for the human health system and agriculture, mostly because of antifungal resistance, emergence new pathogens adverse effects, pressing scientific world exploration compounds. Therefore, aim this work was to synthesize study activity against plant fungi a class hybrid bis-(imidazole/benzimidazole)-pyridine salt derivatives. Methods: The synthesis derivatives performed using both conventional thermal heating ultrasound irradiation methods. Results: use has advantages dramatic decrease in reaction time and, consequently, notable acceleration rate, remarkable consumed energy higher yields. five strains determined by disk diffusion method minimum inhibitory concentration. Conclusions: tested manifest good strains. Some compounds have very quasi-nonselective pathogenic fungi, some cases close control drug fluconazole, respectively, many agents commercially used protection.

Language: Английский

Citations

0
New insides into chimeric and hybrid azines derivatives with antifungal activity DOI
Tiberius Balaeş,

Camelia Georgiana Marandis,

Violeta Mangalagiu

et al.

Future Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 16(11), P. 1163 - 1180

Published: May 28, 2024

During the last decades, five or six member rings azaheterocycles compounds appear to be an extremely valuable source of antifungal agents. Their use seems a very attractive solution in therapy and overcome resistance agriculture. The present review highlights main results obtained field hybrid chimeric azine (especially pyridine, quinoline, phenanthroline, bypyridine, naphthyridine their fused derivatives) derivatives presented scientific literature from 10 years, with emphasis on activity mentioned compounds. A special attention was played azole–azine class, having view high potential azoles.

Language: Английский

Citations

1
Inhibition of apoptosis and biofilm formation in Candida auris by click-synthesized triazole-bridged quinoline derivatives DOI Creative Commons
Mohmmad Younus Wani, Vartika Srivastava, Waleed A. El‐Said

et al.

RSC Advances, Journal Year: 2024, Volume and Issue: 14(29), P. 21190 - 21202

Published: Jan. 1, 2024

Candida auris, a recent addition to the species, poses significant threat with its association numerous hospital outbreaks globally, particularly affecting immunocompromised individuals. Given resistance existing antifungal therapies, there is pressing need for innovative treatments. In this study, novel triazole bridged quinoline derivatives were synthesized and evaluated their activity against C. auris. The most promising compound, QT7, demonstrated exceptional efficacy minimum inhibitory concentration (MIC) fungicidal (MFC) of 0.12 μg mL-1 0.24 mL-1, respectively. Additionally, QT7 effectively disrupted mature biofilms, inhibiting them by 81.98% ± 8.51 89.57 5.47 at MFC 2× values, Furthermore, induced cellular apoptosis in dose-dependent manner, supported various apoptotic markers such as phosphatidylserine externalization, mitochondrial depolarization, reduced cytochrome c oxidase activity. Importantly, exhibited low hemolytic activity, highlighting potential further investigation. physicochemical properties compound suggest lead drug candidate, warranting exploration discovery efforts auris infections.

Language: Английский

Citations

1
Garlic-Derived Quorum Sensing Inhibitors: A Novel Strategy Against Fungal Resistance DOI Creative Commons
Na Li, Junli Zhang, Fei Yu

et al.

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 6413 - 6426

Published: Dec. 1, 2024

In recent years, the incidence of fungal infections has been rising annually, especially among immunocompromised populations, posing a significant challenge to public health. Although antifungal medications provide some relief, escalating problem resistance sharply curtails their effectiveness, presenting an urgent clinical dilemma that demands immediate attention. Research shown is closely related quorum sensing (QS), and QS inhibitors (QSIs) are considered effective solution this issue. Garlic, as natural QSI, demonstrated effects in inhibiting growth, preventing biofilm formation, enhancing immunity, combating resistance. This study explores potential garlic mitigating drug identifies its key role mechanism, these findings offer new perspective for treatment infections, addressing increasingly severe However, application still faces several challenges, such ensuring standardization active ingredient extraction, well issues safety stability. Future research should focus on mechanism promote interdisciplinary collaboration develop more natural, effective, safe QSI drugs like garlic, while actively conducting trials validate efficacy safety. Additionally, incorporating advanced technologies nanotechnology enhance stability targeting, comprehensive strategy infections. Overall, Our provides scientific evidence supporting novel lays groundwork development future QSIs therapeutic use. It offers insights, particularly populations drug-resistant strains.

Language: Английский

Citations

0
In vitro antifungal activity of MMV Pathogen Box® compounds, alone or in combination with antifungal drugs, against mucormycosis agents DOI Creative Commons
Fernando Almeida‐Silva,

Pedro Henrique Tenório-Alvarenga,

Raiane Valle da Costa

et al.

Current Research in Microbial Sciences, Journal Year: 2024, Volume and Issue: 6, P. 100242 - 100242

Published: Jan. 1, 2024

Mucormycosis is a severe fungal infection that demands immediate and decisive intervention upon suspicion. The causative agents of mucormycosis exhibit inherent resistance to echinocandins voriconazole, their in vitro susceptibility terbinafine highly variable species-specific. Considering these factors the limitations currently available antifungal therapies, identification novel antifungals with potent activity against paramount importance. This study aims identify compounds from MMV Pathogen Box® presenting selected evaluate potential synergistic effects when combined drugs. A screening was conducted, isolated or combination sub-inhibitory concentrations amphotericin B, isavuconazole posaconazole, Rhizopus oryzae strain. Hits screenings were further evaluated eight Mucoralean strains for minimal inhibitory fungicidal concentration determinations confirm interactions using checkerboard method. Ultrastructural studies performed scanning electron microscopy. MMV675968 exhibited R. All but one spp. presented MIC ≤ 1 μg/mL, geometric mean 0.78 μg/mL observed across all isolates this compound, which did not change significantly cellular structure fungus. drugs revealed six additional potentially active strain, two them demonstrated proven synergism through assay. first Zigomycetes highlights promising new treatment options future.

Language: Английский

Citations

0