Antifungal Activity and Mechanism of Action of the Co(III) Coordination Complexes With Diamine Chelate Ligands Against Reference and Clinical Strains of Candida spp.

The high mortality rate of candidemia and the limited option for the treatment of Candida spp. infection have been driving the search for new molecules with antifungal property. In this context, coordination complexes of metal ions and ligands appear to be important. Therefore, this study aimed to synthesize two new copper(II) complexes with 2-thiouracil and 6-methyl-2-thiouracil ligands and to evaluate their mutagenic potential and antifungal activity against Candida. The complexes were synthesized and characterized by infrared vibrational spectroscopy, CHN elemental analysis, UV-Vis experiments and ESI-HRMS spectrometry studies. The antifungal activity was evaluated by broth microdilution against 21 clinical isolates of Candida species. The mutagenic potential was evaluated by the Ames test. The complexes were Cu(Bipy)Cl2(thiouracil) (Complex 1) and Cu(Bipy)Cl2(6-methylthiouracil) (Complex 2). Complex 1 showed fungicidal and fungistatic activities against all isolates. Furthermore, the Minimum Inhibitory Concentration (MIC) from 31 to 125 µg/mL and inhibition percentage of 9.9% against the biofilms of C. krusei and C. glabrata were demonstrated. At the concentrations tested, complex 1 exhibited no mutagenic potential. Complex 2 and the free ligands exhibited no antifungal activity at the concentrations evaluated. Since complex 1 presented antifungal activity against all the tested isolates and no mutagenic potential, it could be proposed as a potential new drug for anti-Candida therapy.

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Ibuprofen Antifungal Activity on Both Planktonic and Biofilm Forms of Fluconazole-Resistant Candida spp. Strains and its Mechanism of Action Evaluated by Flow Cytometry

International Journal of Current Microbiology and Applied Sciences ◽

10.20546/ijcmas.2018.703.242 ◽

2018 ◽

Vol 7 (03) ◽

pp. 2063-2073

Author(s):

Letícia S. Sampaio ◽

Cecília R. da Silva ◽

Rosana S. Campos ◽

Francisca B.S.A. do Nascimento ◽

João B.A. Neto ◽

...

Keyword(s):

Flow Cytometry ◽

Antifungal Activity ◽

Mechanism Of Action ◽

Candida Spp ◽

Fluconazole Resistant

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Antifungal Activity of N-(4-Halobenzyl)amides against Candida spp. and Molecular Modeling Studies

International Journal of Molecular Sciences ◽

10.3390/ijms23010419 ◽

2021 ◽

Vol 23 (1) ◽

pp. 419

Author(s):

Yunierkis Perez-Castillo ◽

Ricardo Carneiro Montes ◽

Cecília Rocha da Silva ◽

João Batista de Andrade Neto ◽

Celidarque da Silva Dias ◽

...

Keyword(s):

Antifungal Activity ◽

Benzoic Acid ◽

Mechanism Of Action ◽

Fungal Infections ◽

Redox Balance ◽

Inhibitory Effect ◽

Candida Spp ◽

Cellular Processes ◽

Antifungal Action ◽

Dynamics Simulations

Fungal infections remain a high-incidence worldwide health problem that is aggravated by limited therapeutic options and the emergence of drug-resistant strains. Cinnamic and benzoic acid amides have previously shown bioactivity against different species belonging to the Candida genus. Here, 20 cinnamic and benzoic acid amides were synthesized and tested for inhibition of C. krusei ATCC 14243 and C. parapsilosis ATCC 22019. Five compounds inhibited the Candida strains tested, with compound 16 (MIC = 7.8 µg/mL) producing stronger antifungal activity than fluconazole (MIC = 16 µg/mL) against C. krusei ATCC 14243. It was also tested against eight Candida strains, including five clinical strains resistant to fluconazole, and showed an inhibitory effect against all strains tested (MIC = 85.3–341.3 µg/mL). The MIC value against C. krusei ATCC 6258 was 85.3 mcg/mL, while against C. krusei ATCC 14243, it was 10.9 times smaller. This strain had greater sensitivity to the antifungal action of compound 16. The inhibition of C. krusei ATCC 14243 and C. parapsilosis ATCC 22019 was also achieved by compounds 2, 9, 12, 14 and 15. Computational experiments combining target fishing, molecular docking and molecular dynamics simulations were performed to study the potential mechanism of action of compound 16 against C. krusei. From these, a multi-target mechanism of action is proposed for this compound that involves proteins related to critical cellular processes such as the redox balance, kinases-mediated signaling, protein folding and cell wall synthesis. The modeling results might guide future experiments focusing on the wet-lab investigation of the mechanism of action of this series of compounds, as well as on the optimization of their inhibitory potency.

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Ocotea glomerata (Nees) Mez Extract and Fractions: Chemical Characterization, Anti-Candida Activity and Related Mechanism of Action

Antibiotics ◽

10.3390/antibiotics9070394 ◽

2020 ◽

Vol 9 (7) ◽

pp. 394

Author(s):

Mayara Nunes Vitor Anjos ◽

Luiz Nascimento de Araújo-Neto ◽

Maria Daniela Silva Buonafina ◽

Rejane Pereira Neves ◽

Edson Rubhens de Souza ◽

...

Keyword(s):

Antifungal Activity ◽

Cell Viability ◽

Mechanism Of Action ◽

Methanol Extract ◽

Fungal Infections ◽

Synergistic Effects ◽

Chemical Characterization ◽

Ros Generation ◽

Candida Spp ◽

Minimal Inhibitory Concentrations

Background: Opportunistic fungal infections are increasingly common, with Candida albicans being the most common etiological agent; however, in recent years, episodes of candidiasis caused by non-albicans Candida species have emerged. Plants belonging to the Lauraceae family have shown remarkable antifungal effects. This study assessed the anti-Candida activity of Ocotea glomerata extracts and fractions, time of death and the synergistic effects with conventional antifungals. The possible mechanism of action was also addressed. Methods: Minimal inhibitory concentrations (MIC) were determined by broth microdilution technique, and the mechanism of action was assessed by ergosterol, sorbitol, cell viability, reactive oxygen species (ROS) generation and phosphatidylserine externalization tests. Results: All the tested extracts evidenced antifungal activity, but the methanol extract was revealed to be the most effective (MIC = 3.12 μg/mL) on C. krusei. The combination of methanol extract with ketoconazole and fluconazole revealed a synergistic effect for C. krusei and C. albicans, respectively. Fractions 1 and 5 obtained from the methanol extract had fungicidal activity, mainly against C. krusei. Methanol extract did not reveal effects by ergosterol and sorbitol assays; however, it led to an increase in intracellular ROS levels, decreased cell viability, and consequently, cell death. Conclusion: O. glomerata methanol extract may be viewed as a rich source of biomolecules with antifungal activity against Candida spp.

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Synthesis and Antifungal Activity of Metal Complexes Containing Dichloro-Tetramorpholino-Cyclophosphazatriene

Metal-Based Drugs ◽

10.1155/mbd.1998.287 ◽

1998 ◽

Vol 5 (5) ◽

pp. 287-294 ◽

Cited By ~ 3

Author(s):

Cornelia Guran ◽

Mihai Barboiu ◽

Paula Diaconescu ◽

Vlad Iluc ◽

Mihaela Bojin ◽

...

Keyword(s):

Antifungal Activity ◽

Chemical Analysis ◽

Metal Complexes ◽

Mechanism Of Action ◽

Divalent Cations ◽

Ergosterol Biosynthesis ◽

Candida Spp ◽

Minimum Inhibitory Concentrations ◽

Physico Chemical ◽

Elemental Chemical Analysis

Metal complexes of dichloro-tetramorpholino-cyclophosphazatriene containing divalent cations such as Ni(II), Co(II), and Mn(II) have been prepared and characterised by standard physico-chemical procedures (elemental chemical analysis, IR and UV-VIS spectra, conductimetric measurement). The newly synthesised compounds possessed antifungal activity against Aspergillus and Candida spp., some of them showing effects comparable to ketoconazole (with minimum inhibitory concentrations in the range of 2- 30 μg/mL) but being generally less active as compared to the azole. Best activity was detected against C. albicans, and worst activity against A. niger. The mechanism of action of these compounds probably involves inhibition of ergosterol biosynthesis, and interaction with lanosterol-14-α-demethylase (CYP51A1), since reduced amounts of ergosterol were evidenced by means of HPLC in cultures of the sensitive strain A. niger treated with some of these inhibitors.

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Antifungal Activity, Mode of Action, Docking Prediction and Anti-biofilm Effects of (+)-β-pinene Enantiomers against Candida spp.

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666181115103104 ◽

2019 ◽

Vol 18 (29) ◽

pp. 2481-2490 ◽

Cited By ~ 6

Author(s):

Ana Cláudia de Macêdo Andrade ◽

Pedro Luiz Rosalen ◽

Irlan Almeida Freires ◽

Luciana Scotti ◽

Marcus Tulius Scotti ◽

...

Keyword(s):

Antifungal Activity ◽

Mode Of Action ◽

Candida Spp ◽

Activity Mode

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Evaluation of Antifungal Activity by Mixed Oxide Metallic Nanocomposite against Candida spp.

Processes ◽

10.3390/pr9050773 ◽

2021 ◽

Vol 9 (5) ◽

pp. 773

Author(s):

Ayodeji Precious Ayanwale ◽

Brenda Lizbeth Estrada-Capetillo ◽

Simón Yobanny Reyes-López

Keyword(s):

Antifungal Activity ◽

Antimicrobial Agents ◽

Mononuclear Cells ◽

Promising Result ◽

Sol Gel ◽

Group Analysis ◽

Candida Spp ◽

Human Mononuclear Cells ◽

Viability Study ◽

High Doses

High doses of antimicrobial agents are a huge threat due to the increasing number of pathogenic organisms that are becoming resistant to antimicrobial agents. This resistance has led to a search for alternatives. Therefore, this study presents the synthesis and characterization of ZrO2-Ag2O nanoparticles (NPs) by sol-gel. The NPs were analyzed by dynamic light scattering (DLS), UV-visible (UV-vis), Raman and scanning electron microscopy (SEM). The NPs were later evaluated for their antifungal effects against Candidaalbicans, Candida dubliniensis, Candida glabrata, and Candida tropicalis, using disc diffusion and microdilution methods, followed by the viability study. The DLS showed sizes for ZrO2 76 nm, Ag2O 50 nm, and ZrO2-Ag2O samples between 14 and 42 nm. UV-vis shows an absorption peak at 300 nm for ZrO2 and a broadband for Ag2O NPs. Raman spectra were consistent with factor group analysis predictions. SEM showed spherically shaped NPs. The antifungal activity result suggested that ZrO2-Ag2O NPs were effective against Candida spp. From the viability study, there was no significance difference in viability as a function of time and concentration on human mononuclear cells. This promising result can contribute toward the development of alternative therapies to treat fungal diseases in humans.

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The Impact of Gelatin on the Pharmaceutical Characteristics of Fucoidan Microspheres with Posaconazole

Materials ◽

10.3390/ma14154087 ◽

2021 ◽

Vol 14 (15) ◽

pp. 4087

Author(s):

Marta Szekalska ◽

Aleksandra Citkowska ◽

Magdalena Wróblewska ◽

Katarzyna Winnicka

Keyword(s):

Antifungal Activity ◽

Drug Release ◽

Spray Drying ◽

Fungal Infections ◽

Drug Loading ◽

High Surface ◽

Vaginal Fluid ◽

Sustained Drug Release ◽

Candida Spp ◽

The Impact

Fungal infections and invasive mycoses, despite the continuous medicine progress, are an important globally therapeutic problem. Multicompartment dosage formulations (e.g., microparticles) ensure a short drug diffusion way and high surface area of drug release, which as a consequence can provide improvement of therapeutic efficiency compared to the traditional drug dosage forms. As fucoidan is promising component with wide biological activity per se, the aim of this study was to prepare fucospheres (fucoidan microparticles) and fucoidan/gelatin microparticles with posaconazole using the one-step spray-drying technique. Pharmaceutical properties of designed fucospheres and the impact of the gelatin addition on their characteristics were evaluated. An important stage of this research was in vitro evaluation of antifungal activity of developed microparticles using different Candida species. It was observed that gelatin presence in microparticles significantly improved swelling capacity and mucoadhesiveness, and provided a sustained POS release. Furthermore, it was shown that gelatin addition enhanced antifungal activity of microparticles against tested Candida spp. strains. Microparticles formulation GF6, prepared by the spray drying of 20% fucoidan, 5% gelatin and 10% Posaconazole, were characterized by optimal mucoadhesive properties, high drug loading and the most sustained drug release (after 8 h 65.34 ± 4.10% and 33.81 ± 5.58% of posaconazole was dissolved in simulated vaginal fluid pH 4.2 or 0.1 M HCl pH 1.2, respectively).

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Development of a Solid Dispersion of Nystatin with Maltodextrin as a Carrier Agent: Improvements in Antifungal Efficacy against Candida spp. Biofilm Infections

Pharmaceuticals ◽

10.3390/ph14050397 ◽

2021 ◽

Vol 14 (5) ◽

pp. 397

Author(s):

Carlos Benavent ◽

Carlos Torrado-Salmerón ◽

Santiago Torrado-Santiago

Keyword(s):

Antifungal Activity ◽

Solid Dispersions ◽

Particle Size Analysis ◽

Size Analysis ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Candida Spp ◽

Microbiological Techniques ◽

Characterization Studies ◽

Candida Albicans Biofilms

The aim of this study was to improve the treatment of Candida albicans biofilms through the use of nystatin solid dispersions developed using maltodextrins as a hyperosmotic carrier. Characterization studies by differential scanning calorimetry, X-ray diffraction, dissolution studies, and particle size analysis were performed to evaluate changes in nystatin crystallinity. Antifungal activity and anti-biofilm efficacy were assessed by microbiological techniques. The results for nystatin solid dispersions showed that the enhancement of antifungal activity may be related to the high proportions of maltodextrins. Anti-biofilm assays showed a significant reduction (more than 80%) on biofilm formation with SD-N:MD [1:6] compared to the nystatin reference suspension. The elaboration process and physicochemical properties of SD-N:MD [1:6] could be a promising strategy for treatment of Candida biofilms.

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Orodispersible Film Loaded with Enterococcus faecium CRL183 Presents Anti-Candida albicans Biofilm Activity In Vitro

Pharmaceutics ◽

10.3390/pharmaceutics13070998 ◽

2021 ◽

Vol 13 (7) ◽

pp. 998

Author(s):

Virgínia Barreto Lordello ◽

Andréia Bagliotti Meneguin ◽

Sarah Raquel de Annunzio ◽

Maria Pía Taranto ◽

Marlus Chorilli ◽

...

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Enterococcus Faecium ◽

Potato Starch ◽

Oral Candidiasis ◽

Candida Spp ◽

Sem Images ◽

Control Film ◽

In Vitro Antifungal Activity

Background: Probiotic bacteria have been emerging as a trustworthy choice for the prevention and treatment of Candida spp. infections. This study aimed to develop and characterize an orodispersible film (ODF) for delivering the potentially probiotic Enterococcus faecium CRL 183 into the oral cavity, evaluating its in vitro antifungal activity against Candida albicans. Methods and Results: The ODF was composed by carboxymethylcellulose, gelatin, and potato starch, and its physical, chemical, and mechanical properties were studied. The probiotic resistance and viability during processing and storage were evaluated as well as its in vitro antifungal activity against C. albicans. The ODFs were thin, resistant, and flexible, with neutral pH and microbiologically safe. The probiotic resisted the ODF obtaining process, demonstrating high viability (>9 log10 CFU·g−1), up to 90 days of storage at room temperature. The Probiotic Film promoted 68.9% of reduction in fungal early biofilm and 91.2% in its mature biofilm compared to the group stimulated with the control film. Those results were confirmed through SEM images. Conclusion: The probiotic ODF developed is a promising strategy to prevent oral candidiasis, since it permits the local probiotic delivery, which in turn was able to reduce C. albicans biofilm formation.

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