Antifungal Activity of 3′-Deoxyadenosine (Cordycepin)

ABSTRACT The antifungal activity of the nucleoside analog 3′-deoxyadenosine (cordycepin) was studied in a murine model of invasive candidiasis. When protected from deamination by either deoxycoformycin or coformycin, both of which are adenosine deaminase inhibitors, cordycepin exhibited potent antifungal efficacy, as demonstrated by prolongation of survival and a decrease in CFU in the kidneys of mice treated with cordycepin plus an adenosine deaminase inhibitor. The antifungal effect was seen with three different Candidaisolates: Candida albicans 64, a relatively fluconazole-resistant clinical isolate of C. albicans (MIC, 16 μg/ml), and the fluconazole-resistant Candida krusei. Cordycepin and related compounds may provide another avenue for the discovery of clinically useful antifungal drugs.

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Synergistic Antifungal Activity of Chitosan with Fluconazole against Candida albicans, Candida tropicalis, and Fluconazole-Resistant Strains

Molecules ◽

10.3390/molecules25215114 ◽

2020 ◽

Vol 25 (21) ◽

pp. 5114

Author(s):

Wei-Hsuan Lo ◽

Fu-Sheng Deng ◽

Chih-Jung Chang ◽

Ching-Hsuan Lin

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Candida Tropicalis ◽

Inhibitory Effect ◽

Antifungal Drugs ◽

Drug Resistant ◽

Combinational Treatment ◽

Fluconazole Resistant ◽

Resistant Strains ◽

Drug Resistant Strains

(1) Background: Few antifungal drugs are currently available, and drug-resistant strains have rapidly emerged. Thus, the aim of this study is to evaluate the effectiveness of the antifungal activity from a combinational treatment of chitosan with a clinical antifungal drug on Candida albicans and Candida tropicalis. (2) Methods: Minimum inhibitory concentration (MIC) tests, checkerboard assays, and disc assays were employed to determine the inhibitory effect of chitosan with or without other antifungal drugs on C. albicans and C. tropicalis. (3) Results: Treatment with chitosan in combination with fluconazole showed a great synergistic fungicidal effect against C. albicans and C. tropicalis, but an indifferent effect on antifungal activity when challenged with chitosan-amphotericin B or chitosan-caspofungin simultaneously. Furthermore, the combination of chitosan and fluconazole was effective against drug-resistant strains. (4) Conclusions: These findings provide strong evidence that chitosan in combination with fluconazole is a promising therapy against two Candida species and its drug-resistant strains.

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Antifungal Activity of Thai Cajuput Oil and Its Effect on Efflux-Pump Gene Expression in Fluconazole-Resistant Candida albicans Clinical Isolates

International Journal of Microbiology ◽

10.1155/2020/5989206 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Pitchayaphong Keereedach ◽

Karnjana Hrimpeng ◽

Khaemaporn Boonbumrung

Keyword(s):

Gene Expression ◽

Candida Albicans ◽

Antifungal Activity ◽

Efflux Pump ◽

Clinical Problem ◽

Antifungal Drugs ◽

Clinical Isolates ◽

Common Mechanism ◽

Fluconazole Resistant ◽

Resistant Strains

Candidiasis caused by the fluconazole-resistant opportunistic pathogen Candida albicans is an intractable clinical problem that threatens immunocompromised or normal individuals. The most common mechanism of fluconazole resistance in C. albicans is the failure of cells to accumulate the drug due to increased expression of the efflux proteins encoded by the CDR1, CDR2, and MDR1 genes. Because the number of current antifungal drugs is limited, it is necessary to develop new therapeutic strategies. This study aimed to evaluate the antifungal activity of Thai Cajuput oil, its synergism with fluconazole, and its effect on efflux-pump gene expression in fluconazole-resistant C. albicans clinical isolates. Thus, we first detected the efflux-pump genes in fourteen resistant strains by PCR. The frequencies of the CDR1, CDR2, and MDR1 genes were 68.75%, 62.5%, and 87.5%, respectively, and these efflux-pump genes were distributed in three distinct patterns. Subsequently, the antifungal activity of Thai Cajuput oil was assessed by broth macrodilution and its synergism with fluconazole was evaluated by the checkerboard assay. The changes in the expression levels of CDR1, CDR2, and MDR1 after treatment with Thai Cajuput oil were analyzed by qRT-PCR. The MICs and MFCs of Thai Cajuput oil ranged from 0.31 to 1.25 μl/ml and 0.63 to 1.25 μl/ml, respectively, and its activity was defined as fungicidal activity. The MICs of the combination of Thai Cajuput oil and fluconazole were much lower than the MICs of the individual drugs. Interestingly, sub-MICs of Thai Cajuput oil significantly reduced the MDR1 expression level in resistant strains P < 0.05 . Our study suggests that Thai Cajuput oil can be used to create new potential combination therapies to combat the antifungal resistance of C. albicans.

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Ibuprofen Potentiates theIn VivoAntifungal Activity of Fluconazole against Candida albicans Murine Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05056-14 ◽

2015 ◽

Vol 59 (7) ◽

pp. 4289-4292 ◽

Cited By ~ 13

Author(s):

Sofia Costa-de-Oliveira ◽

Isabel M. Miranda ◽

Ana Silva-Dias ◽

Ana P. Silva ◽

Acácio G. Rodrigues ◽

...

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Murine Model ◽

Resistant Strain ◽

Efflux Pump ◽

Systemic Infection ◽

New Approach ◽

Content Type ◽

Fungal Burden ◽

Fluconazole Resistant

ABSTRACTCandida albicansis the most prevalent cause of fungemia worldwide. Its ability to develop resistance in patients receiving azole antifungal therapy is well documented. In a murine model of systemic infection, we show that ibuprofen potentiates fluconazole antifungal activity against a fluconazole-resistant strain, drastically reducing the fungal burden and morbidity. The therapeutic combination of fluconazole with ibuprofen may constitute a new approach for the management of antifungal therapeutics to reverse the resistance conferred by efflux pump overexpression.

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Efficacy of Novel Schiff base Derivatives as Antifungal Compounds in Combination with Approved Drugs Against Candida Albicans

Medicinal Chemistry ◽

10.2174/1573406415666181203115957 ◽

2019 ◽

Vol 15 (6) ◽

pp. 648-658 ◽

Cited By ~ 1

Author(s):

Manzoor Ahmad Malik ◽

Shabir Ahmad Lone ◽

Parveez Gull ◽

Ovas Ahmad Dar ◽

Mohmmad Younus Wani ◽

...

Keyword(s):

Schiff Base ◽

Candida Albicans ◽

Antifungal Activity ◽

Fungal Infections ◽

Total Sterol ◽

Antifungal Drugs ◽

New Drugs ◽

Ergosterol Biosynthesis ◽

Dependent Manner ◽

Schiff Base Derivatives

Background: The increasing incidence of fungal infections, especially caused by Candida albicans, and their increasing drug resistance has drastically increased in recent years. Therefore, not only new drugs but also alternative treatment strategies are promptly required. Methods: We previously reported on the synergistic interaction of some azole and non-azole compounds with fluconazole for combination antifungal therapy. In this study, we synthesized some non-azole Schiff-base derivatives and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drugs- fluconazole (FLC) and amphotericin B (AmB) against four drug susceptible, three FLC resistant and three AmB resistant clinically isolated Candida albicans strains. To further analyze the mechanism of antifungal action of these compounds, we quantified total sterol contents in FLC-susceptible and resistant C. albicans isolates. Results: A pyrimidine ring-containing derivative SB5 showed the most potent antifungal activity against all the tested strains. After combining these compounds with FLC and AmB, 76% combinations were either synergistic or additive while as the rest of the combinations were indifferent. Interestingly, none of the combinations was antagonistic, either with FLC or AmB. Results interpreted from fractional inhibitory concentration index (FICI) and isobolograms revealed 4-10-fold reduction in MIC values for synergistic combinations. These compounds also inhibit ergosterol biosynthesis in a concentration-dependent manner, supported by the results from docking studies. Conclusion: The results of the studies conducted advocate the potential of these compounds as new antifungal drugs. However, further studies are required to understand the other mechanisms and in vivo efficacy and toxicity of these compounds.

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Biodegradable polymers-based nanoparticles to enhance the antifungal efficacy of fluconazole against Candida albicans

Current Pharmaceutical Biotechnology ◽

10.2174/1389201022666210708105142 ◽

2021 ◽

Vol 22 ◽

Author(s):

Noha Saleh ◽

Soha Elshaer ◽

Germeen Girgis

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Encapsulation Efficiency ◽

Water Solubility ◽

In Vitro Release ◽

Double Emulsion ◽

Dilution Method ◽

Ft Ir ◽

Antifungal Efficacy

Background: Fluconazole (FLZ), a potent antifungal medication, is characterized by poor water solubility that reduced its antifungal efficacy. Objective: This study aimed to prepare FLZ-loaded polymeric nanoparticles (NPs) by using different polymers and techniques as a mean of enhancing the antifungal activity of FLZ. Methods: NP1, NP2, and NP3 were prepared by the double emulsion/solvent evaporation method using PLGA, PCL, and PLA, respectively. The ionotropic pre-gelation technique was applied to prepare an alginate/chitosan-based formulation (NP4). Particle size, zeta potential, encapsulation efficiency, and loading capacity were characterized. FT-IR spectra of FLZ, the polymers, and the prepared NPs were estimated. NP4 was selected for further in-vitro release evaluation. The broth dilution method was used to assess the antifungal activity of NP4 using a resistant clinical isolate of Candida albicans. Results: The double emulsion method produced smaller-sized particles (<390 nm) but with much lower encapsulation efficiency (< 12%). Alternatively, the ionic gelation method resulted in nanosized particles with a markedly higher encapsulation efficiency of about 40%. The FT-IR spectroscopy confirmed the loading of the FLZ molecules in the polymeric network of the prepared NPs. The release profile of NP4 showed a burst initial release followed by a controlled pattern up to 24 hours with a higher percent released relative to the free FLZ suspension. NP4 was able to reduce the value of MIC of FLZ by 20 times. Conclusion: The antifungal activity of FLZ against C. albicans was enhanced markedly via its loading in the alginate/chitosan-based polymeric matrix of NP4.

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Antifungal activity of components used for decontamination of dental prostheses on the growth of Candida albicans

Revista de Odontologia da UNESP ◽

10.1590/rou.2014.018 ◽

2014 ◽

Vol 43 (2) ◽

pp. 137-142 ◽

Cited By ~ 2

Author(s):

Cíntia Lima Gouveia ◽

Isabelle Cristine Melo Freire ◽

Maria Luísa de Alencar e Silva Leite ◽

Rebeca Dantas Alves Figueiredo ◽

Leopoldina de Fátima Dantas de Almeida ◽

...

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Sodium Bicarbonate ◽

Fungal Growth ◽

Antifungal Effect ◽

Dental Prostheses ◽

Diffusion Technique ◽

Zones Of Inhibition ◽

And Control

Introduction: The effectiveness of antimicrobial solutions employed in dental prosthesis decontamination is still uncertain. Aim: To evaluate the antifungal activity of cleaners used in the decontamination of dental prostheses on the growth of Candida albicans. Material and method: The evaluated products were: Corega Tabs(r) (S1), Sodium Hypochlorite 1% (S2), Sodium Bicarbonate 1% (S3), Hydrogen Peroxide 1% (S4), Chlorhexidine Digluconate 0.12% - Periogard (r) (S5), Mouthrinse based on essential oils - Listerine(r) (S6), essential oil from Rosmarinus officinalis (rosemary) at concentrations of 1% (S7) and 2% (S8). The antifungal activity of the products was evaluated by agar diffusion technique and the determination of microbial death curve of samples of C. albicans (ATCC 90028) in concentration 1.5 × 106 CFU/mL. The tests were performed in triplicate and statistical analysis was made by ANOVA Two-Way and Tukey tests, with the confidence level of 95%. Result: The average of the zones of inhibition growth, in millimeters, obtained for the products were: 0.0 (S1), 44.7 (S2), 0.0 (S3), 21.6 (S4), 10.0 (S5), 6.1 (S6), 0.0 (S7) and 2.4 (S8). Considering the determination of microbial death curve, all products showed a statistical difference (p<0.01) from control (0.85% sodium chloride) and S3 groups. Fungal growth less than 2×104 CFU/mL and an accentuation of the microbial death curve were observed after 30 minutes, with exception for S3 and control groups. Conclusion: The studied compounds, with the exception of Sodium Bicarbonate, have antifungal effect against C. albicans, which contribute for dental prostheses hygiene.

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Synthesis, Characterization and in Vitro Antifungal Effect of Some Butyltin(IV) N-substituted 2-aminoethanethiolates

Metal-Based Drugs ◽

10.1155/mbd.2001.165 ◽

2001 ◽

Vol 8 (3) ◽

pp. 165-169 ◽

Cited By ~ 2

Author(s):

A. Smicka ◽

V. Buchta ◽

K. Handlir

Keyword(s):

Candida Glabrata ◽

Pathogenic Fungi ◽

Trichophyton Mentagrophytes ◽

Candida Krusei ◽

Antifungal Drugs ◽

Antifungal Effect ◽

Absidia Corymbifera ◽

Structure Activity ◽

Trichosporon Beigelii

Six new N-substituted di- and tributyltin 2-aminoethanethiolates (cysteaminates) have been prepared and characterised by H1, C13 and S119n NMR spectroscopy. All these compounds exhibit a good in vitro antifungal effect against selected types of human pathogenic fungi (Candida albicans, Candida krusei, Candida tropicalis, Candida glabrata, Trichosporon beigelii, Aspergillus fumigatus, Absidia corymbifera, Trichophyton mentagrophytes) and their activity is comparable with that of some antifungal drugs commonly used in the clinical use like ketoconazole. The structure-activity relationships in these compounds are discussed.

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Novel Antifungal Compounds Discovered in Medicines for Malaria Venture’s Malaria Box

mSphere ◽

10.1128/msphere.00537-17 ◽

2018 ◽

Vol 3 (2) ◽

Cited By ~ 7

Author(s):

Eric H. Jung ◽

David J. Meyers ◽

Jürgen Bosch ◽

Arturo Casadevall

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Cryptococcus Neoformans ◽

Fungal Pathogens ◽

Pathogenic Fungi ◽

Cryptococcus Gattii ◽

Antifungal Drugs ◽

Resistant Bacteria ◽

Animal Cells ◽

Malaria Box

ABSTRACTSimilarities in fungal and animal cells make antifungal discovery efforts more difficult than those for other classes of antimicrobial drugs. Currently, there are only three major classes of antifungal drugs used for the treatment of systemic fungal diseases: polyenes, azoles, and echinocandins. Even in situations where the offending fungal organism is susceptible to the available drugs, treatment courses can be lengthy and unsatisfactory, since eradication of infection is often very difficult, especially in individuals with impaired immunity. Consequently, there is a need for new and more effective antifungal drugs. We have identified compounds with significant antifungal activity in the Malaria Box (Medicines for Malaria Ventures, Geneva, Switzerland) that have higher efficacy than some of the currently used antifungal drugs. Our best candidate, MMV665943 (IUPAC name 4-[6-[[2-(4-aminophenyl)-3H-benzimidazol-5-yl]methyl]-1H-benzimidazol-2-yl]aniline), here referred to as DM262, showed 16- to 32-fold-higher activity than fluconazole againstCryptococcus neoformans. There was also significant antifungal activity in other fungal species with known antifungal resistance, such asLomentospora prolificansandCryptococcus gattii. Antifungal activity was also observed against a common fungus,Candida albicans. These results are important because they offer a potentially new class of antifungal drugs and the repurposing of currently available therapeutics.IMPORTANCEMuch like the recent increase in drug-resistant bacteria, there is a rise in antifungal-resistant strains of pathogenic fungi. There is a need for novel and more potent antifungal therapeutics. Consequently, we investigated a mixed library of drug-like and probe-like compounds with activity inPlasmodiumspp. for activity against two common fungal pathogens,Cryptococcus neoformansandCandida albicans, along with two less common pathogenic species,Lomentospora prolificansandCryptococcus gattii. We uncover a previously uncharacterized drug with higher broad-spectrum antifungal activity than some current treatments. Our findings may eventually lead to a compound added to the arsenal of antifungal therapeutics.

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In Vitro Antifungal Activities of a Series of Dication-Substituted Carbazoles, Furans, and Benzimidazoles

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.10.2503 ◽

1998 ◽

Vol 42 (10) ◽

pp. 2503-2510 ◽

Cited By ~ 58

Author(s):

Maurizio Del Poeta ◽

Wiley A. Schell ◽

Christine C. Dykstra ◽

Susan K. Jones ◽

Richard R. Tidwell ◽

...

Keyword(s):

Antimicrobial Activity ◽

Candida Albicans ◽

Fusarium Solani ◽

Antifungal Agents ◽

Antifungal Drugs ◽

Inhibitory Compounds ◽

Wide Range ◽

Fluconazole Resistant ◽

Resistant Strains

ABSTRACT Aromatic dicationic compounds possess antimicrobial activity against a wide range of eucaryotic pathogens, and in the present study an examination of the structures-functions of a series of compounds against fungi was performed. Sixty-seven dicationic molecules were screened for their inhibitory and fungicidal activities againstCandida albicans and Cryptococcus neoformans. The MICs of a large number of compounds were comparable to those of the standard antifungal drugs amphotericin B and fluconazole. Unlike fluconazole, potent inhibitory compounds in this series were found to have excellent fungicidal activities. The MIC of one of the most potent compounds against C. albicans was 0.39 μg/ml, and it was the most potent compound against C. neoformans (MIC, ≤0.09 μg/ml). Selected compounds were also found to be active againstAspergillus fumigatus, Fusarium solani,Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. Since some of these compounds have been safely given to animals, these classes of molecules have the potential to be developed as antifungal agents.

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