Antifungal efficacy of atorvastatin-containing emulgel in the treatment of oral and vulvovaginal candidiasis

2020 ◽  
Author(s):  
Ari Soares de Oliveira Neto ◽  
Israel Lucas Antunes Souza ◽  
Maria Eliza Samuel Amorim ◽  
Thalita de Freitas Souza ◽  
Vinicius Novaes Rocha ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Drug Repositioning ◽  
Oral Candidiasis ◽  
Vulvovaginal Candidiasis ◽  
Antifungal Drugs ◽  
Sterol Synthesis ◽  
In Vitro Tests

Abstract Drug repositioning has been an important ally in the search for new antifungal drugs. Statins are drugs that act to prevent sterol synthesis in both humans and fungi and for this reason they are promissory candidates to be repositioned to treat mycoses. In this study we evaluated the antifungal activity of atorvastatin by in vitro tests to determine the minimum inhibitory concentration against azole resistant Candida albicans and its mechanisms of action. Moreover, the efficacy of both atorvastatin-loaded oral and vaginal emulgels (0.75%, 1.5% and 3% w/w) was evaluated by means of in vivo experimental models of oral and vulvovaginal candidiasis, respectively. The results showed that atorvastatin minimal inhibitory concentration against C. albicans was 31.25 μg/ml. In oral candidiasis experiments, the group treated with oral emulgel containing 3.0% atorvastatin showcased total reduction in fungal load after nine days of treatment. Intravaginal delivery atorvastatin emulgel showed considerable effectiveness at the concentration of 3% (65% of fungal burden reduction) after nine days of treatment. From these findings, it is possible to assert that atorvastatin may be promising for drug repositioning towards the treatment of these opportunistic mycoses. Lay Summary Atorvastatin is a statin drug that presents antifungal activity. This study showed that atorvastatin-containing oral and vaginal emulgels were able to treat vulvovaginal and oral candidiasis of infected animal model. Therefore, we showcased that atorvastatin may be a possible therapeutic agent in order to be a used to control opportunistic mucosal fungal infections caused by Candida albicans.

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

2019 ◽  
Vol 15 (6) ◽  
pp. 648-658 ◽  
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.

scholarly journals ANTI-CANDIDA ALBICANS ACTIVITY OF THE ASSOCIATION OF CITRONELAL WITH ANFOTERICIN B OR WITH CETOCONAZOLE

2019 ◽  
Vol 16 (31) ◽  
pp. 250-257
Author(s):  
Patrícia Duarte Costa SILVA ◽  
Brenda Lavínia Calixto dos SANTOS ◽  
Gustavo Lima SOARES ◽  
Wylly Araújo de OLIVEIRA
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Mortality Rates ◽  
New Drugs ◽  
High Morbidity ◽  
Isolated Species

Fungal infections caused by species of the genus Candida are responsible for high morbidity and mortality rates, mainly affecting immunocompromised individuals. Among fungi, Candida albicans is the most frequently isolated species of clinical specimens. A problem associated with increased resistance of pathogenic fungi to the agents used in the therapeutic regimen and the limited number of drugs to cure these infections. As a result, the search for new drugs with antifungal activity has become increasingly important. The aim of this study is to study the antifungal activity of citronellal alone and in combination with amphotericin B or ketoconazole. The Minimal Inhibitory Concentration of citronellal, amphotericin B and ketoconazole against strains of Candida albicans were evaluated by the microdilution technique, and the Minimum Fungicide Concentration of citronellal against the same strains was also performed. Through the checkerboard methodology the effect of the combination of citronelal with amphotericin B or with ketoconazole was determined. This study showed that the association of citronellal with ketoconazole was shown to be an additive against one of the strains of C. albicans and indifferent to another strain. While the combined activity of citronellal and amphotericin B demonstrated an indifferent effect on the strains tested.

scholarly journals The Effects of Tormentic Acid and Extracts from Callistemon citrinus on Candida albicans and Candida tropicalis Growth and Inhibition of Ergosterol Biosynthesis in Candida albicans

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Chido Bvumbi ◽  
Godloves Fru Chi ◽  
Marc Y. Stevens ◽  
Molly Mombeshora ◽  
Stanley Mukanganyama
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Candida Tropicalis ◽  
Methanol Extract ◽  
Fungal Infections ◽  
Water Extract ◽  
Antifungal Drugs ◽  
Ergosterol Content ◽  
Broth Microdilution Method ◽  
Tormentic Acid

Candida albicans and Candida tropicalis are the leading causes of human fungal infections worldwide. There is an increase in resistance of Candida pathogens to existing antifungal drugs leading to a need to find new sources of antifungal agents. Tormentic acid has been isolated from different plants including Callistemon citrinus and has been found to possess antimicrobial properties, including antifungal activity. The study aimed to determine the effects of tormentic and extracts from C. citrinus on C. albicans and C. tropicalis and a possible mode of action. The extracts and tormentic acid were screened for antifungal activity using the broth microdilution method. The growth of both species was inhibited by the extracts, and C. albicans was more susceptible to the extract compared to C. tropicalis. The growth of C. albicans was inhibited by 80% at 100 μg/ml of both the DCM: methanol extract and the ethanol: water extract. Tormentic acid reduced the growth of C. albicans by 72% at 100 μg/ml. The effects of the extracts and tormentic acid on ergosterol content in C. albicans were determined using a UV/Vis scanning spectrophotometer. At concentrations of tormentic acid of 25 μg/ml, 50 μg/ml, 100 μg/ml, and 200 μg/ml, the content of ergosterol was decreased by 22%, 36%, 48%, and 78%, respectively. Similarly, the DCM: methanol extract at 100 μg/ml and 200 μg/ml decreased the content by 78% and 88%, respectively. A dose-dependent decrease in ergosterol content was observed in cells exposed to miconazole with a 25 μg/ml concentration causing a 100% decrease in ergosterol content. Therefore, tormentic acid inhibits the synthesis of ergosterol in C. albicans. Modifications of the structure of tormentic acid to increase its antifungal potency may be explored in further studies.

scholarly journals Artemisinins, New Miconazole Potentiators Resulting in Increased Activity against Candida albicans Biofilms

2014 ◽  
Vol 59 (1) ◽  
pp. 421-426 ◽  
Author(s):  
Kaat De Cremer ◽  
Ellen Lanckacker ◽  
Tanne L. Cools ◽  
Marijke Bax ◽  
Katrijn De Brucker ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Drug Repositioning ◽  
Antibiofilm Activity ◽  
Content Type ◽  
Structural Homologues ◽  
Increased Activity ◽  
Candida Albicans Biofilms ◽  
Concentration Indices

ABSTRACTMucosal biofilm-related fungal infections are very common, and the incidence of recurrent oral and vulvovaginal candidiasis is significant. As resistance to azoles (the preferred treatment) is occurring, we aimed at identifying compounds that increase the activity of miconazole againstCandida albicansbiofilms. We screened 1,600 compounds of a drug-repositioning library in combination with a subinhibitory concentration of miconazole. Synergy between the best identified potentiators and miconazole was characterized by checkerboard analyses and fractional inhibitory concentration indices. Hexachlorophene, pyrvinium pamoate, and artesunate act synergistically with miconazole in affectingC. albicansbiofilms. Synergy was most pronounced for artesunate and structural homologues thereof. No synergistic effect could be observed between artesunate and fluconazole, caspofungin, or amphotericin B. Our data reveal enhancement of the antibiofilm activity of miconazole by artesunate, pointing to potential combination therapy consisting of miconazole and artesunate to treatC. albicansbiofilm-related infections.

Antifungal Activity of Peppermint Oil against Candida Albicans Isolated from Urine Samples

2019 ◽  
Vol 12 (4) ◽  
pp. 4611-4615
Author(s):  
Noura Berakda ◽  
Abdulkarim Radwan
Keyword(s):  
Candida Albicans ◽  
Urinary Tract ◽  
Antifungal Activity ◽  
Fungal Infections ◽  
In Vitro Study ◽  
Inhibition Zone ◽  
Antifungal Drugs ◽  
University Hospital ◽  
Peppermint Oil

Fungal infections with candida species are an important cause of morbidity and mortality. Situation is further worsened by increasing resistance to antifungal drugs. In this study, we sought to investigate the antifungal activity of peppermint oil against candida albicans of urinary tract candidiasis in females from Syria. An in vitro study was carried out using the following Candida albicans strains involved in urinary tract candidiasis using well diffusion (WD) testing: Candida albicans (ATCC 90028) and 15 strains were compiled from Aleppo university Hospital. It was taken from women having urinary tract candidiasis. The antifungal activity of peppermint oil was determined in the form of inhibition zone using antifungal assay agar WD testing. In all experiments, the obtained results indicated that peppermint oil has inhibitory effects on Candida albicans (ATCC 90028) and some 15 strains. This study showed that peppermint oil was active against the tested Candida albicans strains. Peppermint oil was more effective against Candida albicans compared to fluconazole. Peppermint oil may have potential for use in the development of clinically useful antifungal preparations. Therefore, peppermint oil might be highly effective in the natural prevention treatment of urinary tract candidiasis.

scholarly journals High-Throughput Screening of a Collection of Known Pharmacologically Active Small Compounds for Identification of Candida albicans Biofilm Inhibitors

2013 ◽  
Vol 57 (8) ◽  
pp. 3681-3687 ◽  
Author(s):  
Samuel A. Siles ◽  
Anand Srinivasan ◽  
Christopher G. Pierce ◽  
José L. Lopez-Ribot ◽  
Anand K. Ramasubramanian
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Biofilm Formation ◽  
High Throughput Screening ◽  
Fungal Infections ◽  
Rapid Development ◽  
Unmet Need ◽  
Antifungal Drugs ◽  
Content Type ◽  
Pharmacologically Active

ABSTRACTCandida albicansis the most common etiologic agent of systemic fungal infections with unacceptably high mortality rates. The existing arsenal of antifungal drugs is very limited and is particularly ineffective againstC. albicansbiofilms. To address the unmet need for novel antifungals, particularly those active against biofilms, we have screened a small molecule library consisting of 1,200 off-patent drugs already approved by the Food and Drug Administration (FDA), the Prestwick Chemical Library, to identify inhibitors ofC. albicansbiofilm formation. According to their pharmacological applications that are currently known, we classified these bioactive compounds as antifungal drugs, as antimicrobials/antiseptics, or as miscellaneous drugs, which we considered to be drugs with no previously characterized antifungal activity. Using a 96-well microtiter plate-based high-content screening assay, we identified 38 pharmacologically active agents that inhibitC. albicansbiofilm formation. These drugs were subsequently tested for their potency and efficacy against preformed biofilms, and we identified three drugs with novel antifungal activity. Thus, repurposing FDA-approved drugs opens up a valuable new avenue for identification and potentially rapid development of antifungal agents, which are urgently needed.

scholarly journals ANTIFUNGAL ACTIVITY OF THE ASSOCIATION OF CARVACROL WITH AMPHOTERICIN B OR WITH KETOCONAZOLE

2019 ◽  
Vol 16 (31) ◽  
pp. 12-17
Author(s):  
Gustavo Lima SOARES ◽  
Brenda Lavínia Calixto dos SANTOS ◽  
Brenna Ravena Araújo LUZ ◽  
Wylly Araújo de OLIVEIRA
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Aspergillus Species ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Antifungal Action

Aspergillus species are a cause of a high number of fungal infections of difficult treatment, presenting an expressive number of deaths due to the complications in the severe cases of infection. The objective was to evaluate the antifungal action of carvacrol against Aspergillus species, as well as to evaluate the interactions when associated with amphotericin B or ketoconazole. The antifungal activity of carvacrol was evaluated by the broth microdilution method. The combinations of the substances were performed by the checkerboard methodology, to determine the Index of Fractional Inhibitory Concentration. Carvacrol showed antifungal activity against all Aspergillus strains used in the trials. In combinations of substances, only a combination of carvacrol and amphotericin B presented satisfactory results. Combinations of carvacrol and ketoconazole have not shown good. It is concluded that carvacrol is a good candidate for the antifungal drug because of its good activity against Aspergillus demonstrated in the present study, as well as in other studies in the literature. Their combination in vitro with amphotericin B or ketoconazole did not present any advantages over the use of antifungal drugs alone.

scholarly journals Increasing Susceptibility of Drug-Resistant Candida albicans to Fluconazole and Terbinafine by 2(5H)-Furanone Derivative

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 642 ◽  
Author(s):  
Irshad S. Sharafutdinov ◽  
Georgii D. Ozhegov ◽  
Alina E. Sabirova ◽  
Valentina V. Novikova ◽  
Svetlana A. Lisovskaya ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Laser Scanning ◽  
Antifungal Agents ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Drug Resistant ◽  
Drug Resistant Strains

The frequency of mycoses caused by drug-resistant fungal pathogen Candida albicans has increased drastically over the last two decades. The spread of drug-resistant strains, along with the limitations of currently available antifungals, complicates the management of fungal infections, thereby representing great challenges for clinical healthcare. Among various antimicrobial pharmacophores, 2(5H)-furanone derivatives have demonstrated antimicrobial, antifungal, and antibiofilm activities. In this study, we report the antifungal activity of the 2(5H)-furanone derivative F105, consisting of three pharmacophores, namely chlorinated 2(5H)-furanone, sulfonyl group, and l-menthol moiety. Although exhibiting moderate antifungal activity alone with the minimum inhibitory concentration (MIC) values of 32–256 μg/mL, F105 potentiates the activity of fluconazole and terbinafine with fractional inhibitory concentration index (FICI) values of 0.27–0.50. Thus, 16 μg/mL of F105 reduced the MICs of these antifungals against fluconazole-resistant C. albicans isolates four-fold, achieving similar values as for the intermediately susceptible phenotype. Confocal laser scanning microscopy revealed that the fluorescent 2(5H)-furanone derivative F145 was also able to penetrate through biofilms formed by C. albicans. Indeed, in the presence of F105, even sub-MIC concentrations of both fluconazole and terbinafine led to significant reduction of C. albicans CFUs in the mature biofilm. Thus, F105 appears to be a promising candidate for the development of novel antifungal agents as well as enhancers of current antifungal agents, particularly for the treatment of drug-resistant C. albicans infections.

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

Pharmaceutics ◽  
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.

Spilanthol as a promising antifungal alkylamide for the treatment of vulvovaginal candidiasis

2021 ◽  
Author(s):  
Rodrigo L Fabri ◽  
Jhamine C O Freitas ◽  
Ari S O Lemos ◽  
Lara M Campos ◽  
Irley O M Diniz ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Cell Membrane ◽  
Multidrug Resistant ◽  
Fungal Strain ◽  
Vulvovaginal Candidiasis ◽  
Biofilm Matrix

Abstract Spilanthol is a bioactive alkylamide from the native Amazon plant species, Acmella oleracea. However, antifungal activities of spilanthol and its application to the therapeutic treatment of candidiasis remains to be explored. This study sought to evaluate the in vitro and in vivo antifungal activity of spilanthol previously isolated from A. oleracea (spilanthol(AcO)) against Candida albicans ATCC® 10231™, a multidrug-resistant fungal strain. Microdilution methods were used to determine inhibitory and fungicidal concentrations of spilanthol(AcO). In planktonic cultures, the fungal growth kinetics, yeast cell metabolic activity, cell membrane permeability and cell wall integrity were investigated. The effect of spilanthol(AcO) on the proliferation and adhesion of fungal biofilms was evaluated by whole slide imaging and scanning electron microscopy. The biochemical composition of the biofilm matrix was also analyzed. In parallel, spilanthol(AcO) was tested in vivo in an experimental vulvovaginal candidiasis model. Our in vitro analyses in C. albicans planktonic cultures detected a significant inhibitory effect of spilanthol(AcO), which affects both yeast cell membrane and cell wall integrity, interfering with the fungus growth. C. albicans biofilm proliferation and adhesion, as well as, carbohydrates and DNA in biofilm matrix were reduced after spilanthol(AcO) treatment. Moreover, infected rats treated with spilanthol(AcO) showed consistent reduction of both fungal burden and inflammatory processes compared to the untreated animals. Altogether, our findings demonstrated that spilanthol(AcO) is an bioactive compound against planktonic and biofilm forms of a multidrug resistant C. albicans strain. Furthermore, spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans. Lay Abstract This study sought to evaluate the antifungal activity of spilanthol against Candida albicans ATCC® 10 231™, a multidrug-resistant fungal strain. Our findings demonstrated that spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans.

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