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 Non-toxic Cobalt(III) Schiff Base Complexes with Broad Spectrum Antifungal Activity

2020 ◽  
Author(s):  
Angelo Frei ◽  
A. Paden King ◽  
Gabrielle J. Lowe ◽  
Amy K. Cain ◽  
Francesca L. Short ◽  
...  
Keyword(s):  
Schiff Base ◽  
Antifungal Activity ◽  
Broad Spectrum ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Schiff Base Complexes ◽  
In Vivo Studies

Resistance to currently available antifungal drugs has quietly been on the rise but overshadowed by the alarming spread of antibacterial resistance. There is a striking lack of attention to the threat of drug resistant fungal infections, with only a handful of new drugs currently in development. Given that metal complexes have proven to be useful new chemotypes in the fight against diseases such as cancer, malaria, and bacterial infections, it stands to reason to explore their possible utility in treating fungal infections. Herein we report a series of cobalt(III) Schiff base complexes with broad spectrum antifungal activity. Some of these complexes (1-3) show minimum inhibitory concentrations (MIC) in the low micro- to nanomolar range against a series of Candida and Cryptococcus yeasts. Additionally, we demonstrate that these compounds show no cytotoxicity against both bacterial and human cells. Finally, we report first in vivo toxicity data on these compounds in Galleria mellonella, showing that doses as high as 266 mg/kg are tolerated without adverse effects, paving the way for further in vivo studies of these complexes. <br>

scholarly journals Non-toxic Cobalt(III) Schiff Base Complexes with Broad Spectrum Antifungal Activity

2020 ◽  
Author(s):  
Angelo Frei ◽  
A. Paden King ◽  
Gabrielle J. Lowe ◽  
Amy K. Cain ◽  
Francesca L. Short ◽  
...  
Keyword(s):  
Schiff Base ◽  
Antifungal Activity ◽  
Broad Spectrum ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Schiff Base Complexes ◽  
In Vivo Studies

Resistance to currently available antifungal drugs has quietly been on the rise but overshadowed by the alarming spread of antibacterial resistance. There is a striking lack of attention to the threat of drug resistant fungal infections, with only a handful of new drugs currently in development. Given that metal complexes have proven to be useful new chemotypes in the fight against diseases such as cancer, malaria, and bacterial infections, it stands to reason to explore their possible utility in treating fungal infections. Herein we report a series of cobalt(III) Schiff base complexes with broad spectrum antifungal activity. Some of these complexes (1-3) show minimum inhibitory concentrations (MIC) in the low micro- to nanomolar range against a series of Candida and Cryptococcus yeasts. Additionally, we demonstrate that these compounds show no cytotoxicity against both bacterial and human cells. Finally, we report first in vivo toxicity data on these compounds in Galleria mellonella, showing that doses as high as 266 mg/kg are tolerated without adverse effects, paving the way for further in vivo studies of these complexes. <br>

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.

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 Herbal Extracts with Antifungal Activity Against Candida albicans: A Systematic Review

2020 ◽  
Vol 20 ◽  
Author(s):  
Hsuan Hsu ◽  
Chirag C. Sheth ◽  
Veronica Veses
Keyword(s):  
Systematic Review ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
High Throughput Screening ◽  
Fungal Infections ◽  
Natural Compounds ◽  
New Drugs ◽  
Mentha Piperita ◽  
Herbal Extracts ◽  
Antifungal Activities

Background: In the era of antimicrobial resistance, fungal pathogens are not an exception. Several strategies, including antimicrobial stewardship programs and high throughput screening of new drugs are being implemented. Several recent studies have demonstrated effectiveness of plant compounds with antifungal activity. Objective: In this systematic review we examine the use of natural compounds as a possible avenue to fight fungal infections produced by Candida albicans, the most common human fungal pathogen. Method: Electronic literature searches were conducted through PubMed/MEDLINE, Cochrane, and Science Direct limited to the 5 years. A total of 131 articles were included with 186 plants extracts evaluated. Results: Although the majority of the natural extracts exhibited antifungal activities against C. albicans (both in vivo and in vitro), the strongest antifungal activity was obtained from Lawsonia inermis, Pelargonium graveolens, Camellia sinensis, Mentha piperita, and Citrus latifolia. Conclusion: The main components with proven antifungal activities were phenolic compounds such as gallic acid, thymol, and flavonoids (specially catechin), polyphenols such as tannins, terpenoids and saponins. The incorporation of nanotechnology enhances greatly the antifungal properties of these natural compounds. Further research is needed to fully characterize the composition of all herbal extracts with antifungal activity as well as the mechanisms of action of the active compounds.

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.

scholarly journals Eap1p, an Adhesin That Mediates Candida albicans Biofilm Formation In Vitro and In Vivo

2007 ◽  
Vol 6 (6) ◽  
pp. 931-939 ◽  
Author(s):  
Fang Li ◽  
Michael J. Svarovsky ◽  
Amy J. Karlsson ◽  
Joel P. Wagner ◽  
Karen Marchillo ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Adhesion ◽  
Biofilm Formation ◽  
Fungal Infections ◽  
Gene Dosage ◽  
Venous Catheter ◽  
Flow Chamber ◽  
Dependent Manner

ABSTRACT Candida albicans is the leading cause of systemic fungal infections in immunocompromised humans. The ability to form biofilms on surfaces in the host or on implanted medical devices enhances C. albicans virulence, leading to antimicrobial resistance and providing a reservoir for infection. Biofilm formation is a complex multicellular process consisting of cell adhesion, cell growth, morphogenic switching between yeast form and filamentous states, and quorum sensing. Here we describe the role of the C. albicans EAP1 gene, which encodes a glycosylphosphatidylinositol-anchored, glucan-cross-linked cell wall protein, in adhesion and biofilm formation in vitro and in vivo. Deleting EAP1 reduced cell adhesion to polystyrene and epithelial cells in a gene dosage-dependent manner. Furthermore, EAP1 expression was required for C. albicans biofilm formation in an in vitro parallel plate flow chamber model and in an in vivo rat central venous catheter model. EAP1 expression was upregulated in biofilm-associated cells in vitro and in vivo. Our results illustrate an association between Eap1p-mediated adhesion and biofilm formation in vitro and in vivo.

GROWTH INHIBITORY ACTIVITIES OF THE RHIZOME CRUDE EXTRACT OF Curcuma longa ON THE HUMAN PATHOGENIC FUNGUS Mucor circinelloides

2020 ◽  
Vol 65 (10) ◽  
pp. 82-91
Author(s):  
Phuong Nguyen Anh ◽  
Mai Le Thi Tuyet ◽  
Trung Trieu Anh
Keyword(s):  
Antifungal Activity ◽  
Crude Extract ◽  
Fungal Infections ◽  
Early Stage ◽  
Curcuma Longa ◽  
Pathogenic Fungus ◽  
Mucor Circinelloides ◽  
Antifungal Drugs ◽  
Diffusion Method ◽  
Dilution Method

Mucormycosis is an uncommon but life-threatening invasive fungal infection, mostly occurs in immunocompromised patients. Lacking the appropriate antifungal drugs is one of the reasons that lead to difficulties in the management of mucormycosis. Curcuma longa has been used traditionally and widely to treat various diseases, including fungal infections. In the search for novel antifungal compounds from natural resources, we evaluated the effect of rhizome crude extract of C. longa on Mucor circinelloides – a causal agent of mucormycosis. The results of screening, using broth dilution method and agar-well diffusion method, showed that the C. longa extract exhibited promising antifungal activity against the fungus M. circinelloides. In liquid medium, C. longa extract decreased the ability of spore germination and the speed of hyphae formation of M. circinelloides decreased by up to approximately 70% and 90%, respectively. Besides, in a solid medium, the crude extract presented similar activity with amphotericin B (400 μg\mL) in decreasing the growth of M. circinelloides by nearly 77%. Moreover, the extract of C. longa also likely to induce the yeast-like type of growth of the dimorphic M. circinelloides in the early stage. These results suggest the plant could be a potential source for further study on biochemical components and the mechanism of its antifungal activity.

Sign in / Sign up

Export Citation Format

Share Document