scholarly journals Ibuprofen Antifungal Activity on Both Planktonic and Biofilm Forms of Fluconazole-Resistant Candida spp. Strains and its Mechanism of Action Evaluated by Flow Cytometry

Author(s):  
Letícia S. Sampaio ◽  
Cecília R. da Silva ◽  
Rosana S. Campos ◽  
Francisca B.S.A. do Nascimento ◽  
João B.A. Neto ◽  
...  
2016 ◽  
Vol 60 (6) ◽  
pp. 3551-3557 ◽  
Author(s):  
Anderson Ramos da Silva ◽  
João Batista de Andrade Neto ◽  
Cecília Rocha da Silva ◽  
Rosana de Sousa Campos ◽  
Rose Anny Costa Silva ◽  
...  

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).


RSC Advances ◽  
2016 ◽  
Vol 6 (109) ◽  
pp. 107577-107590 ◽  
Author(s):  
Mohammad Jalal ◽  
Mohammad Azam Ansari ◽  
Arun Kumar Shukla ◽  
Syed G. Ali ◽  
Haris M. Khan ◽  
...  

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


2019 ◽  
Vol 14 (17) ◽  
pp. 1477-1488 ◽  
Author(s):  
Lívia G do AV Sá ◽  
Cecília R da Silva ◽  
Rosana de S Campos ◽  
João B de A Neto ◽  
Letícia S Sampaio ◽  
...  

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.


2020 ◽  
Vol 69 (10) ◽  
pp. 1221-1227
Author(s):  
Lívia Gurgel do Amaral Valente Sá ◽  
Cecília Rocha da Silva ◽  
João Batista de Andrade Neto ◽  
Francisca Bruna Stefany Aires do Nascimento ◽  
Fátima Daiana Dias Barroso ◽  
...  

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.


2021 ◽  
Vol 23 (1) ◽  
pp. 419
Author(s):  
Yunierkis Perez-Castillo ◽  
Ricardo Carneiro Montes ◽  
Cecília Rocha da Silva ◽  
João Batista de Andrade Neto ◽  
Celidarque da Silva Dias ◽  
...  

Fungal infections remain a high-incidence worldwide health problem that is aggravated by limited therapeutic options and the emergence of drug-resistant strains. Cinnamic and benzoic acid amides have previously shown bioactivity against different species belonging to the Candida genus. Here, 20 cinnamic and benzoic acid amides were synthesized and tested for inhibition of C. krusei ATCC 14243 and C. parapsilosis ATCC 22019. Five compounds inhibited the Candida strains tested, with compound 16 (MIC = 7.8 µg/mL) producing stronger antifungal activity than fluconazole (MIC = 16 µg/mL) against C. krusei ATCC 14243. It was also tested against eight Candida strains, including five clinical strains resistant to fluconazole, and showed an inhibitory effect against all strains tested (MIC = 85.3–341.3 µg/mL). The MIC value against C. krusei ATCC 6258 was 85.3 mcg/mL, while against C. krusei ATCC 14243, it was 10.9 times smaller. This strain had greater sensitivity to the antifungal action of compound 16. The inhibition of C. krusei ATCC 14243 and C. parapsilosis ATCC 22019 was also achieved by compounds 2, 9, 12, 14 and 15. Computational experiments combining target fishing, molecular docking and molecular dynamics simulations were performed to study the potential mechanism of action of compound 16 against C. krusei. From these, a multi-target mechanism of action is proposed for this compound that involves proteins related to critical cellular processes such as the redox balance, kinases-mediated signaling, protein folding and cell wall synthesis. The modeling results might guide future experiments focusing on the wet-lab investigation of the mechanism of action of this series of compounds, as well as on the optimization of their inhibitory potency.


2008 ◽  
Vol 54 (11) ◽  
pp. 950-956 ◽  
Author(s):  
Patrícia Pozzatti ◽  
Liliane Alves Scheid ◽  
Tatiana Borba Spader ◽  
Margareth Linde Atayde ◽  
Janio Morais Santurio ◽  
...  

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.


Antibiotics ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 394
Author(s):  
Mayara Nunes Vitor Anjos ◽  
Luiz Nascimento de Araújo-Neto ◽  
Maria Daniela Silva Buonafina ◽  
Rejane Pereira Neves ◽  
Edson Rubhens de Souza ◽  
...  

Background: Opportunistic fungal infections are increasingly common, with Candida albicans being the most common etiological agent; however, in recent years, episodes of candidiasis caused by non-albicans Candida species have emerged. Plants belonging to the Lauraceae family have shown remarkable antifungal effects. This study assessed the anti-Candida activity of Ocotea glomerata extracts and fractions, time of death and the synergistic effects with conventional antifungals. The possible mechanism of action was also addressed. Methods: Minimal inhibitory concentrations (MIC) were determined by broth microdilution technique, and the mechanism of action was assessed by ergosterol, sorbitol, cell viability, reactive oxygen species (ROS) generation and phosphatidylserine externalization tests. Results: All the tested extracts evidenced antifungal activity, but the methanol extract was revealed to be the most effective (MIC = 3.12 μg/mL) on C. krusei. The combination of methanol extract with ketoconazole and fluconazole revealed a synergistic effect for C. krusei and C. albicans, respectively. Fractions 1 and 5 obtained from the methanol extract had fungicidal activity, mainly against C. krusei. Methanol extract did not reveal effects by ergosterol and sorbitol assays; however, it led to an increase in intracellular ROS levels, decreased cell viability, and consequently, cell death. Conclusion: O. glomerata methanol extract may be viewed as a rich source of biomolecules with antifungal activity against Candida spp.


1998 ◽  
Vol 5 (5) ◽  
pp. 287-294 ◽  
Author(s):  
Cornelia Guran ◽  
Mihai Barboiu ◽  
Paula Diaconescu ◽  
Vlad Iluc ◽  
Mihaela Bojin ◽  
...  

Metal complexes of dichloro-tetramorpholino-cyclophosphazatriene containing divalent cations such as Ni(II), Co(II), and Mn(II) have been prepared and characterised by standard physico-chemical procedures (elemental chemical analysis, IR and UV-VIS spectra, conductimetric measurement). The newly synthesised compounds possessed antifungal activity against Aspergillus and Candida spp., some of them showing effects comparable to ketoconazole (with minimum inhibitory concentrations in the range of 2- 30 μg/mL) but being generally less active as compared to the azole. Best activity was detected against C. albicans, and worst activity against A. niger. The mechanism of action of these compounds probably involves inhibition of ergosterol biosynthesis, and interaction with lanosterol-14-α-demethylase (CYP51A1), since reduced amounts of ergosterol were evidenced by means of HPLC in cultures of the sensitive strain A. niger treated with some of these inhibitors.


2021 ◽  
Vol 16 (2) ◽  
pp. 71-81
Author(s):  
Maria AV Holanda ◽  
Cecília R da Silva ◽  
João B de A Neto ◽  
Lívia G do AV Sá ◽  
Francisca BSA do Nascimento ◽  
...  

Aim: The purpose of this study was to evaluate the antifungal activity of midazolam, alone and in association with azoles, against isolates of clinical Candida spp. in planktonic and biofilm form. Materials & methods: The antifungal activity was observed using the broth microdilution technique. Flow cytometry tests were performed to investigate the probable mechanism of action and the comet test and cytotoxicity test were applied to evaluate DNA damage. Results: Midazolam (MIDAZ) showed antifungal activity against planktonic cells (125–250 μg/ml) and reduced the viability of Candida spp. biofilms (125 a 2500 μg/ml). The interaction of MIDAZ against Candida spp. biofilms was observed through scanning electron microscopy, causing alteration of their appearance. Therefore, MIDAZ has antifungal potential against Candida spp.


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