Modulating the Antifungal Activity of Antimycotic Drugs with Farnesol

Introduction. Clinical strains of microorganisms, including opportunistic yeast-like fungi (YLF) of the genus Candida, are resistant to currently used antifungal drugs. In this regard, the search for alternative ways to potentiate the activity of antimicrobial agents in relation to the infectious agent is an important and relevant area of research. The study of combinations of existing antimycotic drugs and a medicinal extract of plant origin – farnesol – is one of the promising approaches in the fight against resistant strains of YLF genus Candida. In our previous studies, farnesol has been shown to exhibit relative activity against YLF Candida albicans biofilms. In this study, we used 6 clinical isolates and one museum strain YLF C. albicans to study the effect of farnesol on the antifungal activity of antimycotic drugs.Aim. To prove that farnesol can increase the antifungal activity of certain antimycotics.Materials and methods. To determine the sensitivity of 7 strains of YLF C. albicans to the antimycotic drugs "Nystatin" (NYS 50 µg), "Ketoconazole" (KET 10 µg), "Clotrimazole" (CTR 10 µg), "Amphotericin B" (AMB 10 µg), "Voriconazole" (VRC 10 µg) disk diffusion test was used. A solution of farnesol in concentrations of 100, 50 and 25 µM in a volume of 25 µl was applied to the disk with the antimycotic drug. Sterile physiological (PhS) solution was used as a control (pH 7.0; V = 25 µl).Results and discussion. In 34.3 % of of experiments we can talk about the modulating effect of farnesol solutions on the antifungal activity of antimycotic drugs. In all these cases, the sensitivity of YLF C. albicans to the antimycotic drug increases.Conclusion. The results of this study provide useful information for understanding the mechanism of QS-molecules action with antifungal activity, as well as they are the basis for the practical application of some QS-molecules in the treatment of infectious diseases caused by YLF of the genus Candida. The study demonstrates that farnesol can be recommended as an active substance that improves the sensitivity of YLF Candida to antimycotic drugs, especially in the case of multi-resistant strains Candida.

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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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Synergistic anticandidal activity of etomidate and azoles against clinical fluconazole-resistant Candida isolates

Future Microbiology ◽

10.2217/fmb-2019-0075 ◽

2019 ◽

Vol 14 (17) ◽

pp. 1477-1488 ◽

Cited By ~ 4

Author(s):

Lívia G do AV Sá ◽

Cecília R da Silva ◽

Rosana de S Campos ◽

João B de A Neto ◽

Letícia S Sampaio ◽

...

Keyword(s):

Antifungal Activity ◽

Antifungal Drugs ◽

Planktonic Cells ◽

Candida Spp ◽

Flow Cytometric ◽

Fluconazole Resistant ◽

Anticandidal Activity ◽

Checkerboard Assay ◽

Resistant Strains ◽

Radical Generation

Aim: The purpose of this study was to evaluate the effect of etomidate alone and in combination with azoles on resistant strains of Candida spp. in both planktonic cells and biofilms. Materials & methods: The antifungal activity of etomidate was assessed by the broth microdilution test; flow cytometric procedures to measure fungal viability, mitochondrial transmembrane potential, free radical generation and cell death; as well detection of DNA damage using the comet assay. The interaction between etomidate and antifungal drugs (itraconazole and fluconazole) was evaluated by the checkerboard assay. Results: Etomidate showed antifungal activity against resistant strains of Candida spp. in planktonic cells and biofilms. Etomidate also presented synergism with fluconazole and itraconazole in planktonic cells and biofilms. Conclusion: Etomidate showed antifungal activity against Candida spp., indicating that it is a possible therapeutic alternative.

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New ethacridine derivatives as the potential antifungal and antibacterial preparations

Medicina ◽

10.3390/medicina43080084 ◽

2007 ◽

Vol 43 (8) ◽

pp. 657 ◽

Cited By ~ 14

Author(s):

Vilma Petrikaite ◽

Eduardas Tarasevišius ◽

Alvydas Pavilonis

Keyword(s):

Antimicrobial Agents ◽

Fungal Infections ◽

Aldehyde Group ◽

Antifungal Drugs ◽

Bacillus Subtilis Atcc ◽

Resistant Strains ◽

Initial Preparation ◽

Limited Spectrum ◽

New Compounds

Until the 20th century fungal infections were rather easy cured, and the need of new antifungal drugs was low. However, low choice of antifungal preparations, their toxicity, limited spectrum of action, and ability to produce resistant strains show the need of new effective medicines for systemic fungal diseases in nowadays. Our goal of research was to synthesize new antimicrobial compounds containing three or more pharmacophores in one molecule. The initial 5-substituted-2-methylmercaptothiazolidin-4-ones were subjected to S-demethylation to yield 2- amino-substituted thiazolidinones. Ethacridine, nitrofuran aldehydes and nitrobenzene aldehyde as pharmacophoric amino or aldehyde group having compounds have been used. Antimicrobial (antifungal) activity of the new compounds was screened in vitro in these bacterial cultures: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, Klebsiella pneumoniae ATCC 33499 and fungal cultures: Candida albicans ATCC 60l93, Candida glabrata, Candida krusei, Candida kefyr ATCC 86l4, Candida tropicalis ATCC 8302, Candida parapsilosis. Results showed that the new compounds were significantly more effective as antimicrobial agents than initial preparation ethacridine. Ethacridine derivatives were not only effective against numerous gram-positive and some gram-negative bacteria, but the spectrum of action has been discovered against fungi. Minimal fungistatic concentration varies in the range l0.0–750 µg/mL and antibacterial concentration is in the range 62.5–l000 µg/mL. Compound 2a having nitrofuryl substituent in the fifth position of tiazolidine cycle was the most active of synthesized ethacridine compounds. The obtained results gave the opportunity to separate the perspective group of potential antiinfective compounds.

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Antimicrobial Susceptibilities of Multidrug-Resistant Campylobacter jejuni and C. coli Strains: In Vitro Activities of 20 Antimicrobial Agents

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00898-09 ◽

2009 ◽

Vol 54 (3) ◽

pp. 1232-1236 ◽

Cited By ~ 45

Author(s):

Mirva Lehtopolku ◽

Ulla-Maija Nakari ◽

Pirkko Kotilainen ◽

Pentti Huovinen ◽

Anja Siitonen ◽

...

Keyword(s):

Campylobacter Jejuni ◽

Antimicrobial Agents ◽

Agar Plate ◽

Inhibition Zone ◽

Multidrug Resistant ◽

Dilution Method ◽

Erythromycin Resistance ◽

Disk Diffusion Test ◽

Resistant Strains

ABSTRACT There is a paucity of information regarding antimicrobial agents that are suitable to treat severe infections caused by multidrug-resistant Campylobacter spp. Our aim was to identify agents that are potentially effective against multiresistant Campylobacter strains. The in vitro activities of 20 antimicrobial agents against 238 Campylobacter strains were analyzed by determining MICs by the agar plate dilution method or the Etest. These strains were selected from 1,808 Campylobacter isolates collected from Finnish patients between 2003 and 2005 and screened for macrolide susceptibility by using the disk diffusion test. The 238 strains consisted of 183 strains with erythromycin inhibition zone diameters of ≤23 mm and 55 strains with inhibition zone diameters of >23 mm. Of the 238 Campylobacter strains, 19 were resistant to erythromycin by MIC determinations (MIC ≥ 16 μg/ml). Given that the resistant strains were identified among the collection of 1,808 isolates, the frequency of erythromycin resistance was 1.1%. All erythromycin-resistant strains were multidrug resistant, with 18 (94.7%) of them being resistant to ciprofloxacin (MIC ≥ 4 μg/ml). The percentages of resistance to tetracycline and amoxicillin-clavulanic acid (co-amoxiclav) were 73.7% and 31.6%, respectively. All macrolide-resistant strains were susceptible to imipenem, meropenem, and tigecycline. Ten (52.6%) multiresistant strains were identified as being Campylobacter jejuni strains, and 9 (47.4%) were identified as being C. coli strains. These data demonstrate that the incidence of macrolide resistance was low but that the macrolide-resistant Campylobacter strains were uniformly multidrug resistant. In addition to the carbapenems, tigecycline was also highly effective against these multidrug-resistant Campylobacter strains in vitro. Its efficacy for the treatment of human campylobacteriosis should be evaluated in clinical trials.

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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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Synthesis, antibacterial and antifungal activity of 1-[4-(1,1,3,3-tetramethylbutyl)phenoxy]-3-dialkylamino-2-propanol quaternary salts

Farmatsevtychnyi zhurnal ◽

10.32352/0367-3057.1.15.04 ◽

2019 ◽

pp. 56-62 ◽

Cited By ~ 1

Author(s):

Y. V. Korotkii ◽

N. A. Vrynchanu ◽

M. L. Dronova ◽

Z. S. Suvorova ◽

O. A. Smertenko

Keyword(s):

Antimicrobial Activity ◽

Antifungal Activity ◽

Antimicrobial Agents ◽

Dilution Method ◽

The Novel ◽

Antibacterial And Antifungal Activity ◽

Antimicrobial Drugs ◽

Quaternary Salts ◽

Resistant Strains ◽

Antibacterial And Antifungal

The emergence and spread of resistant strains of pathogens as well as reduction of the efficacy of current antimicrobial agents requires the development of novel antimicrobial compounds. The aim of the present study was synthesis and evaluation of antimicrobial activity of new arylaliphatic aminopropanols. The objects of the present study were 1-[4-(1,1,3,3-tetramethylbutyl)phenoxy]-3-dialkylamino-2-propanol quaternary salts (compounds I–XIV). Compounds synthesis was carried out by heating of precursor epoxide and excessive amount of appropriate amines in isopropanole, followed by treatment with excess of alkyl halides. Methods of elemental analysis, IR- and PMR-spectroscopy were used for confirmation of chemical structure. Antimicrobial activity against Staphylococcus аureus АTCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa АТСС 27853 and Candida albicans NCTC 885/653 was determined by a broth dilution method and evaluated via minimum inhibitory concentration (MIC). Our investigation of antibacterial and antifungal activity of 1-[4-(1,1,3,3-tetra methylbutyl)phenoxy]-3-dialkylamino-2-propanol quaternary salts showed that compounds possess narrow spectrum, as well as broad spectrum action. Significant antimicrobial activity of the novel aryl aliphatic aminoalcohols indicates their potential usage as a component of new antimicrobial drugs.

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Synthesis of 5-amino-1-aryl-3-methyl-1H-pyrazole-4-carbonitriles, Antifungal Activity and In Silico Analysis

Letters in Organic Chemistry ◽

10.2174/1570178617666200210105246 ◽

2020 ◽

Vol 17 (10) ◽

pp. 779-787

Author(s):

Luciana Terra ◽

Daiane de Jesus Viegas ◽

Alice Maria Rolim Bernardino ◽

Jéssica Venância Faria ◽

Percilene Fazolin Vegi ◽

...

Keyword(s):

Antifungal Activity ◽

Fungal Infections ◽

In Silico Analysis ◽

Single Step ◽

Antifungal Drugs ◽

Candida Spp ◽

Disk Diffusion Test ◽

Chemical Structures ◽

Microdilution Method ◽

Drug Classes

Serious fungal infections are increasing worldwide and have become a great concern in the medical field since antifungal drugs are restricted to a few drug classes. This work aims to evaluate the antifungal activity of a series of 5-amino-1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (1a-g) and to establish a structure-activity relationship (SAR). The synthesis of these compounds was carried out in a single step followed by cyclization in good to excellent yields i.e. 73-94%. The chemical structures were confirmed by melting point, IR, 1H-NMR, 13C-NMR, and HRMS. These seven compounds were submitted to the disk diffusion test against Candida spp. and the active compound was evaluated by means of the microdilution method to determine the minimum inhibitory concentration (MIC). In addition, the stereo electronic descriptors were evaluated and pharmacokinetic and toxicological properties were calculated to predict the potential of these compounds as a drug. All the compounds presented good theoretical physicochemical parameters and one of them showed reasonably good antifungal activity.

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Copper-catalyzed Convenient Synthesis and SAR Studies of Substituted-1,2,3-triazole as Antimicrobial Agents

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180326153322 ◽

2018 ◽

Vol 16 (1) ◽

pp. 3-10

Author(s):

Aniket P. Sarkate ◽

Kshipra S. Karnik ◽

Pravin S. Wakte ◽

Ajinkya P. Sarkate ◽

Ashwini V. Izankar ◽

...

Keyword(s):

Antimicrobial Activity ◽

Antifungal Activity ◽

Antimicrobial Agents ◽

Cycloaddition Reaction ◽

Dipolar Cycloaddition ◽

One Pot ◽

Triazole Derivatives ◽

Sar Studies ◽

Convenient Synthesis ◽

Antibacterial And Antifungal

Background:A novel copper-catalyzed synthesis of substituted-1,2,3-triazole derivatives has been developed and performed by Huisgen 1,3-dipolar cycloaddition reaction of azides with alkynes. The reaction is one-pot multicomponent.Objective:We state the advancement and execution of a methodology allowing for the synthesis of some new substituted 1,2,3-triazole analogues with antimicrobial activity.Methods:A series of triazole derivatives was synthesized by Huisgen 1,3-dipolar cycloaddition reaction of azides with alkynes. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, IR, MS and elemental analysis. All the synthesized compounds were tested for their antimicrobial activity against a series of strains of Bacillus subtilis, Staphylococcus aureus and Escherichia coli for antibacterial activity and against the strains of Candida albicans, Aspergillus flavus and Aspergillus nigar for antifungal activity, respectively.Results and Conclusion:From the antimicrobial data, it was observed that all the newly synthesized compounds showed good to moderate level of antibacterial and antifungal activity.

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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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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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