Antifungal activity of etomidate against growing biofilms of fluconazole-resistant Candida spp. strains, binding to mannoproteins and molecular docking with the ALS3 protein

This study evaluated the effect of etomidate against biofilms of Candida spp. and analysed through molecular docking the interaction of this drug with ALS3, an important protein for fungal adhesion. Three fluconazole-resistant fungi were used: Candida albicans, Candida parapsilosis and Candida tropicalis. Growing biofilms were exposed to etomidate at 31.25–500 µg ml−1. Then, an ALS3 adhesive protein from C. albicans was analysed through a molecular mapping technique, composed of a sequence of algorithms to perform molecular mapping simulation based on classic force field theory. Etomidate showed antifungal activity against growing biofilms of resistant C. albicans, C. parapsilosis and C. tropicalis at all concentrations used in the study. The etomidate coupling analysis revealed three interactions with the residues of interest compared to hepta-threonine, which remained at the ALS3 site. In addition, etomidate decreased the expression of mannoproteins on the surface of C. albicans. These results revealed that etomidate inhibited the growth of biofilms.

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Green synthesis and antifungal activity of Al2O3NPs against fluconazole-resistant Candida spp isolated from a tertiary care hospital

RSC Advances ◽

10.1039/c6ra23365a ◽

2016 ◽

Vol 6 (109) ◽

pp. 107577-107590 ◽

Cited By ~ 15

Author(s):

Mohammad Jalal ◽

Mohammad Azam Ansari ◽

Arun Kumar Shukla ◽

Syed G. Ali ◽

Haris M. Khan ◽

...

Keyword(s):

Antifungal Activity ◽

Green Synthesis ◽

Tertiary Care Hospital ◽

Tertiary Care ◽

Care Hospital ◽

Candida Spp ◽

Fluconazole Resistant

Antifungal activity of ecofriendly and cost effectively prepared Al2O3NPs onCandia alibicans.

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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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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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In vitro activity of essential oils extracted from plants used as spices against fluconazole-resistant and fluconazole-susceptible Candida spp.

Canadian Journal of Microbiology ◽

10.1139/w08-097 ◽

2008 ◽

Vol 54 (11) ◽

pp. 950-956 ◽

Cited By ~ 53

Author(s):

Patrícia Pozzatti ◽

Liliane Alves Scheid ◽

Tatiana Borba Spader ◽

Margareth Linde Atayde ◽

Janio Morais Santurio ◽

...

Keyword(s):

Chemical Composition ◽

Antifungal Activity ◽

Essential Oils ◽

Zingiber Officinale ◽

Retention Indices ◽

Thymus Vulgaris ◽

Candida Spp ◽

Fluconazole Resistant ◽

Rosmarinus Officinalis L

In the present study, the antifungal activity of selected essential oils obtained from plants used as spices was evaluated against both fluconazole-resistant and fluconazole-susceptible Candida spp. The Candida species studied were Candida albicans , Candida dubliniensis , Candida tropicalis , Candida glabrata , and Candida krusei. For comparison purposes, they were arranged in groups as C. albicans, C. dubliniensis, and Candida non-albicans. The essential oils were obtained from Cinnamomum zeylanicum Breyn, Lippia graveolens HBK, Ocimum basilicum L., Origanum vulgare L., Rosmarinus officinalis L., Salvia officinalis L., Thymus vulgaris L., and Zingiber officinale . The susceptibility tests were based on the M27-A2 methodology. The chemical composition of the essential oils was obtained by gas chromatography – mass spectroscopy and by retention indices. The results showed that cinnamon, Mexican oregano, oregano, thyme, and ginger essential oils have different levels of antifungal activity. Oregano and ginger essential oils were found to be the most and the least efficient, respectively. The main finding was that the susceptibilities of fluconazole-resistant C. albicans, C. dubliniensis, and Candida non-albicans to Mexican oregano, oregano, thyme, and ginger essential oils were higher than those of the fluconazole-susceptible yeasts (P < 0.05). In contrast, fluconazole-resistant C. albicans and Candida non-albicans were less susceptible to cinnamon essential oil than their fluconazole-susceptible counterparts (P < 0.05). A relationship between the yeasts’ susceptibilities and the chemical composition of the essential oils studied was apparent when these 2 parameters were compared. Finally, basil, rosemary, and sage essential oils did not show antifungal activity against Candida isolates at the tested concentrations.

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Berberine Antifungal Activity in Fluconazole-Resistant Pathogenic Yeasts: Action Mechanism Evaluated by Flow Cytometry and Biofilm Growth Inhibition in Candida spp.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01846-15 ◽

2016 ◽

Vol 60 (6) ◽

pp. 3551-3557 ◽

Cited By ~ 41

Author(s):

Anderson Ramos da Silva ◽

João Batista de Andrade Neto ◽

Cecília Rocha da Silva ◽

Rosana de Sousa Campos ◽

Rose Anny Costa Silva ◽

...

Keyword(s):

Flow Cytometry ◽

Antifungal Activity ◽

Cryptococcus Neoformans ◽

Fungal Infections ◽

Cell Activity ◽

Candida Spp ◽

Antifungal Effect ◽

Content Type ◽

Broth Microdilution Method ◽

Fluconazole Resistant

The incidence of fungal infections and, in particular, the incidence of fungal antibiotic resistance, which is associated with biofilm formation, have significantly increased, contributing to morbidity and mortality. Thus, new therapeutic strategies need to be developed. In this context, natural products have emerged as a major source of possible antifungal agents. Berberine is a protoberberine-type isoquinoline alkaloid isolated from the roots, rhizomes, and stem bark of natural herbs, such asBerberis aquifolium,Berberis vulgaris,Berberis aristata, andHydrastis canadensis, and ofPhellodendron amurense. Berberine has been proven to have broad antibacterial and antifungal activity. In the present study, the potential antifungal effect of berberine against fluconazole-resistantCandidaandCryptococcus neoformansstrains, as well as against the biofilm form ofCandidaspp., was assessed. The antifungal effect of berberine was determined by a broth microdilution method (the M27-A3 method of the Clinical and Laboratory Standards Institute) and flow cytometry techniques, in which the probable mechanism of action of the compound was also assessed. For biofilm assessment, a colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to determine the susceptibility of sessile cells. The isolates used in the study belonged to the Laboratory of Bioprospection and Experiments in Yeast (LABEL) of the Federal University of Ceará. After 24 and 72 h, fluconazole-resistantCandidaandCryptococcus neoformansstrains showed berberine MICs equal to 8 μg/ml and 16 μg/ml, respectively. Cytometric analysis showed that treatment with berberine caused alterations to the integrity of the plasma and mitochondrial membranes and DNA damage, which led to cell death, probably by apoptosis. Assessment of biofilm-forming isolates after treatment showed statistically significant reductions in biofilm cell activity (P< 0.001).

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Boswellia serrata Extract as an Antibiofilm Agent against Candida spp.

Microorganisms ◽

10.3390/microorganisms10010171 ◽

2022 ◽

Vol 10 (1) ◽

pp. 171

Author(s):

Petr Jaroš ◽

Maria Vrublevskaya ◽

Kristýna Lokočová ◽

Jana Michailidu ◽

Irena Kolouchová ◽

...

Keyword(s):

Antifungal Activity ◽

Candida Species ◽

Biofilm Formation ◽

Candida Parapsilosis ◽

Modern Medicine ◽

Biologically Active ◽

Pathogenic Microorganisms ◽

Boswellic Acid ◽

Candida Spp ◽

Boswellia Serrata

The use of antibiotics or antifungals to control infections caused by pathogenic microorganisms is currently insufficiently effective because of their emerging resistance. Thanks to the ability of microorganisms to form a biofilm and thus increase their resistance to administered drugs even more, modern medicine faces the task of finding novel substances to combat infections caused by them. In this regard, the effects of essential oils or plant extracts are often studied. Among the relatively neglected plants is Boswellia serrata, which has a high content of biologically active boswellic acids. In this study, we focused on one of the most common nosocomial infections, which are caused by Candida species. The most common representative is C. albicans, although the number of infections caused by non-albicans species has recently been increasing. We focused on the antifungal activity of Boswellia serrata extract Bioswellix against planktonic and adhering cells of Candida albicans, Candida parapsilosis and Candida krusei. The antifungal activity against adhering cells was further explored by determining the metabolic activity of cells (MTT) and determining the total amount of biofilm using crystal violet. Boswellic acid-containing plant extract was shown to suppress the growth of a suspension population of all tested Candida species. Boswellia serrata extract Bioswellix was most effective in inhibiting C. albicans biofilm formation.

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Voriconazole-natural latex dressings for treating infected Candida spp. skin ulcers

Future Microbiology ◽

10.2217/fmb-2020-0122 ◽

2020 ◽

Vol 15 (15) ◽

pp. 1439-1452

Author(s):

Thainá V da Silva ◽

Natan R de Barros ◽

Caroline B Costa-Orlandi ◽

Jean L Tanaka ◽

Lincoln G Moro ◽

...

Keyword(s):

Antifungal Activity ◽

Candida Parapsilosis ◽

Natural Rubber Latex ◽

Biological Characterization ◽

Casting Method ◽

Candida Spp ◽

Biological Assays ◽

Skin Ulcers ◽

Interesting Alternative ◽

Dermal Application

Aim: This work aimed to develop a membrane based on voriconazole (VCZ)-loaded natural rubber latex (NRL) for treating infected ulcers with Candida spp. and study their interaction, drug release, antifungal activity against Candida parapsilosis and biological characterization. Materials & methods: VCZ-loaded NRL membrane was produced by casting method. Results: Infrared spectrum showed that the incorporation of VCZ into the NRL membrane maintained its characteristics. Its mechanical properties were considered suitable for dermal application. The VCZ was able to release from NRL membrane, maintaining its antifungal activity against C. parapsilosis, besides did not present hemolytic effects. Conclusion: The VCZ-NRL membrane showed good results in mechanical, antifungal and biological assays, representing an interesting alternative to treatment of infected wound with Candida spp.

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Isoeugenol and Hybrid Acetamides against Candida albicans Isolated from the Oral Cavity

Pharmaceuticals ◽

10.3390/ph13100291 ◽

2020 ◽

Vol 13 (10) ◽

pp. 291

Author(s):

Daianne Medeiros ◽

José Oliveira-Júnior ◽

Jefferson Nóbrega ◽

Laísa Cordeiro ◽

Jeane Jardim ◽

...

Keyword(s):

Candida Albicans ◽

Molecular Docking ◽

Antifungal Activity ◽

Oral Cavity ◽

Docking Study ◽

Molecular Docking Study ◽

Candida Spp ◽

Fungal Cell ◽

Hybrid Molecules

Isougenol is a phytoconstituent found in several essential oils. Since many natural products are potent antimicrobials, the synthesis of hybrid molecules—combining the chemical skeleton of the phytochemical with synthetic groups—can generate substances with enhanced biological activity. Based on this, the objective of this study was to evaluate the antifungal activity of isoeugenol and hybrid acetamides against Candida albicans isolated from the oral cavity. The methodologies used were the determination of minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), action on fungal micromorphology, interaction test with nystatin by the checkerboard method and molecular docking study with important enzymes in the maintenance of fungal viability. The synthetic molecules did not demonstrate significant antifungal activity in vitro. The isoeugenol MIC and MFC varied between 128 and 256 µg/mL, being the phytoconstituent able to interfere in the formation of blastoconid and chlamydoconid structures, important in the pathogenic process of the species. The molecular docking study revealed that isoeugenol is a potential inhibitor of the enzymes 14-α-demethylase and delta-14-sterol reductase, interfering in the fungal cell membrane biosynthesis. Thus, this research provides clearer expectations for future pharmacological studies with isoeugenol and derived molecules, aiming at its therapeutic application against infections caused by Candida spp.

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Synthesis, Molecular Docking Studies, and Antifungal Activity Evaluation of New Benzimidazole-Triazoles as Potential Lanosterol 14α-Demethylase Inhibitors

Journal of Chemistry ◽

10.1155/2017/9387102 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 10

Author(s):

Nafiz Öncü Can ◽

Ulviye Acar Çevik ◽

Begüm Nurpelin Sağlık ◽

Serkan Levent ◽

Büşra Korkut ◽

...

Keyword(s):

Molecular Docking ◽

Antifungal Activity ◽

Active Site ◽

Candida Parapsilosis ◽

Docking Studies ◽

Candida Krusei ◽

Ergosterol Biosynthesis ◽

Molecular Docking Studies ◽

Chemical Structures ◽

Nih 3T3

Due to anticandidal importance of azole compounds, a new series of benzimidazole-triazole derivatives(5a–5s)were designed and synthesized as ergosterol inhibitors. The chemical structures of the target compounds were characterized by spectroscopic methods. The final compounds were screened for antifungal activity againstCandida glabrata(ATCC 90030),Candida krusei(ATCC 6258),Candida parapsilosis(ATCC 22019), andCandida albicans(ATCC 24433). Compounds5iand5sexhibited significant inhibitory activity againstCandidastrains with MIC50values ranging from 0.78 to 1.56 μg/mL. Cytotoxicity results revealed that IC50values of compounds5iand5sagainst NIH/3T3 are significantly higher than their MIC50values. Effect of the compounds5iand5sagainst ergosterol biosynthesis was determined by LC-MS-MS analysis. Both compounds caused a significant decrease in the ergosterol level. The molecular docking studies were performed to investigate the interaction modes between the compounds and active site of lanosterol 14-α-demethylase (CYP51), which is as a target enzyme for anticandidal azoles. Theoretical ADME predictions were also calculated for final compounds.

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Antifungal Activity and Mechanism of Action of Different Parts of Myrtus communis Growing in Saudi Arabia against Candida Spp.

Journal of Nanomaterials ◽

10.1155/2021/3484125 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Abdullah A. Alyousef

Keyword(s):

Saudi Arabia ◽

Natural Products ◽

Antifungal Activity ◽

Candida Glabrata ◽

Candida Parapsilosis ◽

Antifungal Drugs ◽

Root Extract ◽

Myrtus Communis ◽

Leaf Extracts ◽

Candida Spp

Discovering new antifungal drugs from natural products is a key target for the treatment of infections, such as candidiasis and other Candida-related infections. As current therapeutic drugs for the treatment of infections, such as candidiasis and other Candida-related infections, have adverse effects on human health, discovering new antifungal drugs from natural products is urgently needed. The objective of this study was to evaluate the antifungal activity of the methanolic and sodium phosphate buffer extracts derived from various parts of Myrtus communis, a plant that is traditionally used in Saudi Arabia, against Candida albicans (ATCC 10213), Candida glabrata (ATCC 2001), Candida kefyr (ATCC 66028), Candida parapsilosis (ATCC 22019), and Candida tropicalis (ATCC 750). A well diffusion assay was performed to assess the antifungal activity through the measurement of the zone of inhibition. Of the extracts, those extracted with methanol from the roots and leaves displayed strong inhibitory activity against Candida glabrata ( 23.5 ± 0.12 and 20.7 ± 0.22 , respectively), at 50 mg/ml, with 5 mg/ml fluconazole administered as the standard control. The minimal inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values were 12.5 mg/ml and 25 mg/ml for the M. communis root extract and 25 mg/ml and 50 mg/ml for the M. communis leaf extract against Candida glabrata. The results were confirmed by scanning electron microscopy (SEM) imaging of the control and treated strains of Candida glabrata. Based on SEM, these extracts could alter the morphology and cause loss of cell integrity. The effect of M. communis root and leaf extracts on Candida cells was also determined by measuring the absorbance at 260 nm after treatment for 1 h at 37°C. Interestingly, the 260 nm absorbing material was higher in Candida glabrata than in the resistant strain, Candida parapsilosis (ATCC 22019). Based on our findings, the crude methanolic extract of M. communis roots and leaves exhibited good antifungal activity against the Candida glabrata strain. SEM results and estimation of the 260 nm absorbance material proved that the extract might act on the cell wall and cell membrane of Candida cells, further leading to cell death.

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