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1.
Microbiol Spectr ; : e0365223, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38289929

RESUMO

This study aims to analyze the antifungal properties of quinalizarin, a plant-derived compound with proven anticancer effects. Quinalizarin exhibited antifungal activity against opportunistic pathogenic Candida species and Geotrichum capitatum. The treatment with this anthraquinone reduced hyphal growth, inhibited biofilm formation, and damaged mature Candida albicans biofilms. Real-time RT-PCR revealed that quinalizarin downregulated the expression of hyphae-related and biofilm-specific genes. The flow cytometry method used in the study showed that both apoptosis and necrosis were the physiological mechanisms of quinalizarin-induced C. albicans cell death, depending on the dose of the antifungal agent. A further study revealed an increase in the levels of intracellular reactive oxygen species and alterations in mitochondrial membrane potential after treatment with quinalizarin. Finally, quinalizarin was found to have low toxicity in a hemolytic test using human erythrocytes. In conclusion, we have identified quinalizarin as a potential antifungal compound.IMPORTANCEThis article is a study to determine the antifungal activity of quinalizarin (1,2,5,8-tetrahydroxyanthraquinone). Quinalizarin has potential antitumor properties and is effective in different types of tumor cells. The aim of the present study was to prove that quinalizarin can be used simultaneously in the treatment of cancer and in the treatment of intercurrent fungal infections. Quinalizarin was identified as a novel antifungal compound with low toxicity. These results may contribute to the development of a new drug with dual activity in the treatment of cancer-associated candidiasis.

2.
Pharmaceuticals (Basel) ; 17(1)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38256922

RESUMO

The aim of this study was to investigate the antifungal activity of biochanin A (BCA) against planktonic growth and biofilms of six Candida species, including C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, C. auris, and C. krusei. We applied various assays that determined (a) the antimicrobial effect on growth of Candida species, (b) the effect on formation of hyphae and biofilm, (c) the effect on the expression of genes related to hyphal growth and biofilm formation, (d) the influence on cell wall structure, and (e) the effect on cell membrane integrity and permeability. Moreover, disk diffusion tests were used to investigate the effect of a combination of BCA with fluconazole to assess their possible synergistic effect on drug-resistant C. albicans, C. glabrata, and C. auris. Our results showed that the BCA MIC50 values against Candida species ranged between 125 µg/mL and 500 µg/mL, and the MIC90 values were in a concentration range from 250 µg/mL to 1000 µg/mL. The treatment with BCA inhibited adhesion of cells, cell surface hydrophobicity (CSH), and biofilm formation and reduced hyphal growth in all the analyzed Candida species. Real-time qRT-PCR revealed that BCA down-regulated the expression of biofilm-specific genes in C. albicans. Furthermore, physical destruction of C. albicans cell membranes and cell walls as a result of the treatment with BCA was observed. The combination of BCA and fluconazole did not exert synergistic effects against fluconazole-resistant Candida.

3.
Molecules ; 28(3)2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36770861

RESUMO

A new type of silver nanoparticles (AgNPs) was prepared and comprehensively studied. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) analyses indicated that 24 nm AgNPs with narrow size distribution were obtained while Z-potential confirms their good stability. The composites of the obtained AgNPs with nontoxic-nature-inspired hydrogel were formed upon cooling of the aqueous solution AgNPs and C12Ala. The thermal gravimetric analysis (TGA) and the differential scanning calorimetry (DSC) do not show significant shifts in the characteristic temperature peaks for pure and silver-enriched gels, which indicates that AgNPs do not strongly interact with C12Ala fibers, which was also confirmed by SEM. Both AgNPs alone and in the assembly with the gelator C12Ala were almost biologically passive against bacteria, fungus, cancer, and nontumor human cells, as well as zebra-fish embryos. These studies proved that the new inactive AgNPs-doped hydrogels have potential for the application in therapy as drug delivery media.


Assuntos
Hidrogéis , Nanopartículas Metálicas , Animais , Humanos , Hidrogéis/química , Prata/química , Nanopartículas Metálicas/química , Bactérias , Extratos Vegetais/química , Antibacterianos/química
4.
J Med Chem ; 65(20): 13935-13945, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36217958

RESUMO

Infections caused by Candida species have increased significantly in the past decades and are among the leading causes of morbidity and mortality worldwide, resulting in serious public health problems. Currently, conventional antifungals are often ineffective as Candida spp. have developed growing resistance to systemic drugs. Since inorganic metallacarboranes are known to affect cellular events, new derivatives of these abiotic compounds were tested against Candida albicans. Compounds based on cobalt bis-dicarbollide [COSAN] were studied on Candida albicans strains, including a panel of 100 clinical isolates. The presented data prove that metallacarborane derivatives are effective against clinical isolates of Candida albicans, even those resistant to systemic drugs, and show synergistic potential in combination with amphotericin B, and low toxicity against human cells and Danio rerio embryos. This paper is a consequential step in the investigations of the broad spectrum and valuable future medical applications of metallacarboranes, especially in the fight against drug-resistant pathogens.


Assuntos
Antifúngicos , Candida albicans , Humanos , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida , Cobalto , Testes de Sensibilidade Microbiana
5.
Chromosoma ; 131(3): 163-173, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35896680

RESUMO

Due to translocation heterozygosity for all chromosomes in the cell complement, the oyster plant (Tradescantia spathacea) forms a complete meiotic ring. It also shows Rabl-arrangement at interphase, featured by polar centromere clustering. We demonstrate that the pericentromeric regions of the oyster plant are homogenized in concert by three subtelomeric sequences: 45S rDNA, (TTTAGGG)n motif, and TSrepI repeat. The Rabl-based clustering of pericentromeric regions may have been an excellent device to combine the subtelomere-pericentromere sequence migration (via inversions) with the pericentromere-pericentromere DNA movement (via whole arm translocations) that altogether led to the concerted homogenization of all the pericentromeric domains by the subtelomeric sequences. We also show that the repetitive sequence landscape of interstitial chromosome regions contains many loci consisting of Arabidopsis-type telomeric sequence or of TSrepI repeat, and it is extensively heterozygous. However, the sequence arrangement on some chromosomal arms suggest segmental inversions that are fully or partially homozygous, a fact that could be explained if the inversions started to create linkages already in a bivalent-forming ancestor. Remarkably, the subterminal TSrepI loci reside exclusively on the longer arms that could be due to sharing sequences between similarly-sized chromosomal arms in the interphase nucleus. Altogether, our study spotlights the supergene system of the oyster plant as an excellent model to link complex chromosome rearrangements, evolution of repetitive sequences, and nuclear architecture.


Assuntos
Ostreidae , Tradescantia , Animais , DNA Ribossômico/genética , Heterocromatina , Hibridização in Situ Fluorescente , Ostreidae/genética , Sequências Repetitivas de Ácido Nucleico , Tradescantia/genética , Translocação Genética
6.
Fungal Biol ; 126(6-7): 407-420, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35667828

RESUMO

Flavonoids are a diverse group of compounds originating from several natural plant sources. Various biological effects of flavonoids have been reported, including antimicrobial and antifungal activities. In this study, we showed the possibility of using commercial flavonoids, i.e. baicalein and quercetin, based on natural equivalents as compounds with antifungal properties against Candida albicans species. The effects of baicalein and/or quercetin were investigated using reference C. albicans strain and 50 clinical strains isolated from vulvovaginal candidiasis (VVC) patients. Baicalein and quercetin MIC values against C. albicans strains ranged between 0.5 and 256 µg/ml. We observed predominantly indifferent, synergistic, or partially synergistic interactions between both flavonoids and between the flavonoids and fluconazole in the treatment of planktonic cells of the C. albicans strains. Treatment with the flavonoid complex inhibited adhesion and aggregation of cells, cell surface hydrophobicity (CSH), flocculation, biofilm formation and reduced hyphal growth. Real-time RT-PCR revealed that baicalein and quercetin in combination down-regulated the expression of biofilm-specific genes. Finally, we observed increase in the cell membrane permeability of C. albicans and its physical destruction as a result of the synergistic activity of baicalein and quercetin. Our research evidences the effectiveness of baicalein and quercetin applied in combination as potential anti-Candida agents.


Assuntos
Antifúngicos , Candida albicans , Antifúngicos/farmacologia , Biofilmes , Candida , Feminino , Flavanonas , Flavonoides/farmacologia , Genitália Feminina , Humanos , Testes de Sensibilidade Microbiana , Quercetina/farmacologia
7.
Molecules ; 26(24)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34946545

RESUMO

An aqueous solution of sodium citrate stabilized gold nanoparticles (AuNP) in the presence of N-lauroyl-L-alanine (C12ALA) forms a stable gel. The structure of the gel and the distribution profile of AuNP in it were analyzed. Will nanoparticles separated from each other with sodium citrate behave in the same way in solution and trapped in the gel matrix? Will the spatial limitation of solvent molecules aggregate nanoparticles and destroy their homogeneity? These questions are very important from the point of view of the use of gold nanoparticles, trapped in the gel structure as carriers of drugs in the slow-release process. The lack of homogeneity of this distribution will have a major impact on the rate of release of the appropriate amount of therapeutic drug from the matrix. In this work, we attempt to answer these questions. The performed biological assays revealed that both C12ALA and C12ALA-AuNP show an excellent level of biological neutrality. They might be used as a transporting medium for a drug delivery without affecting the drug's activity.


Assuntos
Alanina/análogos & derivados , Portadores de Fármacos , Ouro , Nanopartículas Metálicas , Alanina/química , Alanina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Ouro/química , Ouro/farmacologia , Células HeLa , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico
8.
Materials (Basel) ; 14(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201678

RESUMO

There is a need to search for new antifungals, especially for the treatment of the invasive Candida infections, caused mainly by C. albicans. These infections are steadily increasing at an alarming rate, mostly among immunocompromised patients. The newly synthesized compounds (3a-3k) were characterized by physicochemical parameters and investigated for antimicrobial activity using the microdilution broth method to estimate minimal inhibitory concentration (MIC). Additionally, their antibiofilm activity and mode of action together with the effect on the membrane permeability in C. albicans were investigated. Biofilm biomass and its metabolic activity were quantitatively measured using crystal violet (CV) staining and tetrazolium salt (XTT) reduction assay. The cytotoxic effect on normal human lung fibroblasts and haemolytic effect were also evaluated. The results showed differential activity of the compounds against yeasts (MIC = 0.24-500 µg/mL) and bacteria (MIC = 125-1000 µg/mL). Most compounds possessed strong antifungal activity (MIC = 0.24-7.81 µg/mL). The compounds 3b, 3c and 3e, showed no inhibitory (at 1/2 × MIC) and eradication (at 8 × MIC) effect on C. albicans biofilm. Only slight decrease in the biofilm metabolic activity was observed for compound 3b. Moreover, the studied compounds increased the permeability of the membrane/cell wall of C. albicans and their mode of action may be related to action within the fungal cell wall structure and/or within the cell membrane. It is worth noting that the compounds had no cytotoxicity effect on pulmonary fibroblasts and erythrocytes at concentrations showing anticandidal activity. The present studies in vitro confirm that these derivatives appear to be a very promising group of antifungals for further preclinical studies.

9.
Saudi J Biol Sci ; 28(5): 2925-2932, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34025170

RESUMO

Yarrowia lipolytica as an oleaginous yeast is capable of growing in various non-conventional hydrophobic substrate types, especially industrial wastes. In this study, the content of thiamine (vitamin B1), riboflavin (vitamin B2), pyridoxine (vitamin B6), biotin (vitamin B7) and folic acid (vitamin B9) in the wet biomass of Y. lipolytica strains cultivated in biofuel waste (SK medium), compared to the standard laboratory YPD medium, was assessed. Additionally, the biomass of Y. lipolytica A-101 grown in biofuel waste (SK medium) was dried and examined for B vitamins concentration according to the recommended microbial methods by AOAC Official Methods. The mean values of these vitamins per 100 g of dry weight of Y. lipolytica grown in biofuel waste (SK medium) were as follows: thiamine 1.3 mg/100 g, riboflavin 5.3 mg/100 g, pyridoxine 4.9 mg/100 g, biotin 20.0 µg/100 g, and folic acid 249 µg/100 g. We have demonstrated that the dried biomass is a good source of B vitamins which can be used as nutraceuticals to supplement human diet, especially for people at risk of B vitamin deficiencies in developed countries. Moreover, the biodegradation of biofuel waste by Y. lipolytica is desired for environmental protection.

10.
Molecules ; 25(12)2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32630522

RESUMO

In the light of the increasing occurrence of antifungal resistance, there is an urgent need to search for new therapeutic strategies to overcome this phenomenon. One of the applied approaches is the synthesis of small-molecule compounds showing antifungal properties. Here we present a continuation of the research on the recently discovered anti-Candida albicans agent 4-AN. Using next generation sequencing and transcriptional analysis, we revealed that the treatment of C. albicans with 4-AN can change the expression profile of a large number of genes. The highest upregulation was observed in the case of genes involved in cell stress, while the highest downregulation was shown for genes coding sugar transporters. Real-time PCR analysis revealed 4-AN mediated reduction of the relative expression of genes engaged in fungal virulence (ALS1, ALS3, BCR1, CPH1, ECE1, EFG1, HWP1, HYR1 and SAP1). The determination of the fractional inhibitory concentration index (FICI) showed that the combination of 4-AN with amphotericin B is synergistic. Finally, flow cytometry analysis revealed that the compound induces mainly necrosis in C. albicans cells.


Assuntos
Antifúngicos/farmacologia , Candida albicans/crescimento & desenvolvimento , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Genoma Fúngico , Necrose , Virulência/genética , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/genética , Proteínas Fúngicas/genética , Perfilação da Expressão Gênica
11.
Bioorg Chem ; 99: 103806, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32279038

RESUMO

The optimization and synthesis of new CK2 and CK1 inhibitors are the basis for the development of new therapeutic strategies for the treatment of cancer and neurodegenerative disorders associated with overexpression and abnormal functioning of these enzymes. Triazole derivatives appear to be especially interesting as potential kinase inhibitors. In this context we synthesized a series of 1,2,4-triazolin-5-thione derivatives as CK1γ kinase inhibitors. The antiproliferative activity of synthesized compounds was assessed against cancer cells: human lung adenocarcinoma (A549), human hepatoma (HepG2), and human breast adenocarcinoma (MCF-7). Compound 1 exhibited antiproliferative potency against A549 cancer cells and was characterized by a selective antiproliferative effect. Additionally, this compound has high apoptotic activity against A549, HepG2, MCF-7 cells and induced only slight amount of necrotic cells in these cell lines. In order to decipher the mechanism of anticancer activity of the studied compounds PASS software was used and these compounds were assayed for the inhibition of CK1γ and CK2α kinases. The reported series of 1,2,4-triazolin-5-thiones inhibits CK1γ and CK2α kinases in micromolar range. The most active compound shows activity against isoform γ3 which at concentration of 50 µM reduced the kinase activity by 69% while at 100 µM by 80%. CK2α was found to be less susceptible to the effects of the triazoles tested, as the reduction in kinase activity by 29% was observed for compound 15, and by 27% for compound 1 only at the concentration of 100 µM. The inhibition of CK1γ and CK2α kinases was rationalized using molecular docking.


Assuntos
Antineoplásicos/farmacologia , Caseína Quinase I/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Triazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Caseína Quinase I/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
12.
Antibiotics (Basel) ; 8(4)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683548

RESUMO

Silymarin is a complex of plant-derived compounds obtained from the seed shells of the milk thistle (Silybum marianum). It is used in medicine primarily to protect the liver. The mixture contains mainly flavonolignans, with silybin as a paramount bioactive component of the extract. This article presents the potential health benefits for silymarin as an antifungal drug against five references strains: C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei with MIC (minimum inhibitory concentration) values ranging from 30 to 300 µg/mL. Additionally, this study revealed that the compound suppressed the growth of cells of most of the tested clinical Candida albicans strains with MIC values between 30 and 1200 µg/mL. Based on the fractional inhibitory concentration index (FICI), the combination of silymarin with antifungal drugs caspofungin, fluconazole, and amphotericin B did not significantly change the MIC values for the tested Candida strains. Furthermore, no antagonistic reactions were observed in any combination of drugs. In addition, this substance shows anti-virulence properties including the destabilization of mature biofilm and the inhibition of the secretion of hydrolases. qRT-PCR-based experiments demonstrated that the SAP4 gene involved in virulence was downregulated by silymarin. These results indicate completely new advantages of dietary supplementation with this natural plant extract.

13.
ChemistryOpen ; 8(5): 589-600, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31098338

RESUMO

1,4-Naphthoquinones are an important class of compounds present in a number of natural products. In this study, a new series of 1,4-naphthoquinone derivatives were synthesized. All the synthesized compounds were tested for in vitro antimicrobial activity. In this present investigation, two Gram-positive and five Gram-negative bacterial strains and one pathogenic yeast strain were used to determine the antibacterial activity. Naphthoquinones tested for its antibacterial potencies, among seven of them displayed better antimicrobial activity against Staphylococcus aureus (S. aureus; 30-70 µg/mL). Some of the tested compounds showed moderate to low antimicrobial activity against Pseudomonas aeruginosa (P. aeruginosa) and Salmonella bongori (S. bongori; 70-150 µg/mL). In addition, most active compounds against S. aureus were evaluated for toxicity to human blood cells using a hemolysis assay. For better understanding, reactive oxygen species (ROS) generation, time-kill kinetic study, and apoptosis, necrosis responses were investigated for three representative compounds.

14.
Molecules ; 24(1)2019 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-30609757

RESUMO

Small molecules containing quinone and/or oxime moieties have been found as promising anti-fungal agents. One of them is 4-AN, a recently reported potent anti-Candida compound, which inhibits the formation of hyphae, decreases the level of cellular phosphoproteome, and finally shows no toxicity towards human erythrocytes and zebrafish embryos. Here, further research on 4-AN is presented. The results revealed that the compound: (i) Kills Candida clinical isolates, including these with developed antibiotic resistance, (ii) affects mature biofilm, and (iii) moderately disrupts membrane permeability. Atomic force microscopy studies revealed a slight influence of 4-AN on the cell surface architecture. 4-AN was also shown to inhibit multiple various protein kinases, a characteristic shared by most of the ATP-competitive inhibitors. The presented compound can be used in novel strategies in the fight against candidiasis, and reversible protein phosphorylation should be taken into consideration as a target in designing these strategies.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Oximas/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Quinonas/uso terapêutico , Biofilmes/efeitos dos fármacos , Transporte Biológico , Membrana Celular , Avaliação Pré-Clínica de Medicamentos , Resistência Microbiana a Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Fosforilação , Ligação Proteica , Propriedades de Superfície
15.
Pol J Microbiol ; 67(4): 463-470, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30550232

RESUMO

Candidiasis is the most common opportunistic yeast infection, with Candida albicans as a paramount causative species. (1,3)- ß -D-glucan is one of the three main targets of clinically available antifungal agents used to treat Candida infections. It is one of the most abundant fungal cell wall components. Echinocandins represent the newest class of antifungals affecting cell wall biosynthesis through non-competitive inhibition of (1,3)- ß -D-glucan synthase. Therefore, treatment with echinocandins causes defects in fungal cell integrity. In the present study, similar activity of emodin (6-methyl-1,3,8-trihydroxyanthraquinone) has been revealed. Many reports have already shown the antifungal potential of this pleiotropic molecule, including its activity against C. albicans . The aim of this report was to evaluate the activity of emodin towards a new molecular target, i.e. (1,3)- ß -D-glucan synthase isolated from Candida cells. Moreover, given the identical mechanism of the activity of both molecules, interaction of emodin with caspofungin was determined. The study revealed that emodin reduced (1,3)- ß -D-glucan synthase activity and increased cell wall damage, which was evidenced by both a sorbitol protection assay and an aniline blue staining assay. Furthermore, the synergy testing method showed mainly independence of the action of both tested antifungal agents, i.e. emodin and caspofungin used in combination.Candidiasis is the most common opportunistic yeast infection, with Candida albicans as a paramount causative species. (1,3)-ß-D-glucan is one of the three main targets of clinically available antifungal agents used to treat Candida infections. It is one of the most abundant fungal cell wall components. Echinocandins represent the newest class of antifungals affecting cell wall biosynthesis through non-competitive inhibition of (1,3)-ß-D-glucan synthase. Therefore, treatment with echinocandins causes defects in fungal cell integrity. In the present study, similar activity of emodin (6-methyl-1,3,8-trihydroxyanthraquinone) has been revealed. Many reports have already shown the antifungal potential of this pleiotropic molecule, including its activity against C. albicans. The aim of this report was to evaluate the activity of emodin towards a new molecular target, i.e. (1,3)-ß-D-glucan synthase isolated from Candida cells. Moreover, given the identical mechanism of the activity of both molecules, interaction of emodin with caspofungin was determined. The study revealed that emodin reduced (1,3)-ß-D-glucan synthase activity and increased cell wall damage, which was evidenced by both a sorbitol protection assay and an aniline blue staining assay. Furthermore, the synergy testing method showed mainly independence of the action of both tested antifungal agents, i.e. emodin and caspofungin used in combination.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Caspofungina/metabolismo , Emodina/farmacologia , Glucosiltransferases/antagonistas & inibidores , Candida albicans/enzimologia , Candidíase/tratamento farmacológico , Parede Celular/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana
16.
Saudi Pharm J ; 26(2): 244-252, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30166923

RESUMO

In this study, we applied various assays to reveal new activities of phenylcyanomethylenequinone oxime-4-(hydroxyimino) cyclohexa-2,5-dien-1-ylidene](phenyl)ethanenitrile (4-AN) for potential anti-microbial applications. These assays demonstrated (a) the antimicrobial effect on bacterial and fungal cultures, (b) the effect on the in vitro activity of the kinase CK2, (c) toxicity towards human erythrocytes, the Caco-2 cancer cell line, and embryonic development of Zebrafish. We demonstrated the activity of 4-AN against selected bacteria and Candida spp. The MIC ranging from 4 µg/ml to 125 µg/ml proved effective in inhibition of formation of hyphae and cell aggregation in Candida, which was demonstrated at the cytological level. Noteworthy, 4-AN was found to inhibit the CK2 kinase with moderate potency. Moreover, at low concentrations, it did not exert any evident toxic effects on human erythrocytes, Caco-2 cells, or Zebrafish embryos. 4-AN can be a potential candidate as a novel drug against Candida infections.

17.
J Med Microbiol ; 67(4): 598-609, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29461185

RESUMO

PURPOSE: In this study, we applied various assays to find new activities of 1,4-naphthoquinone derivatives for potential anti-Candida albicans applications. METHODOLOGY: These assays determined (a) the antimicrobial effect on growth/cell multiplication in fungal cultures, (b) the effect on formation of hyphae and biofilm, (c) the influence on cell membrane integrity, (d) the effect on cell morphology using atomic force microscopy, and (e) toxicity against zebrafish embryos. We have demonstrated the activity of these compounds against different Candida species and clinical isolates of C. albicans. KEY FINDINGS: 1,4-Naphthoquinones significantly affected fungal strains at 8-250 mg l-1 of MIC. Interestingly, at concentrations below MICs, the chemicals showed effectiveness in inhibition of hyphal formation and cell aggregation in Candida. Of note, atomic force microscopy (AFM) analysis revealed an influence of the compounds on cell morphological properties. However, at low concentrations (0.8-31.2 mg l-1), it did not exert any evident toxic effects on zebrafish embryos. CONCLUSIONS: Our research has evidenced the effectiveness of 1,4-naphthoquinones as potential anti-Candida agents.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Naftoquinonas/farmacologia , Animais , Antifúngicos/toxicidade , Candida albicans/crescimento & desenvolvimento , Candidíase/microbiologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Hifas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Naftoquinonas/toxicidade , Peixe-Zebra/embriologia
18.
Molecules ; 23(1)2018 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-29346325

RESUMO

A new series of coumarin-1,2,3-triazole conjugates with varied alkyl, phenyl and heterocycle moieties at C-4 of the triazole nucleus were synthesized using a copper(I)-catalysed Huisgen 1,3-dipolar cycloaddition reaction of corresponding O-propargylated coumarin (3) or N-propargylated coumarin (6) with alkyl or aryl azides. Based on their minimal inhibitory concentrations (MICs) against selected microorganisms, six out of twenty-six compounds showed significant antibacterial activity towards Enterococcus faecalis (MIC = 12.5-50 µg/mL). Moreover, the synthesized triazoles show relatively low toxicity against human erythrocytes.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Cumarínicos/síntese química , Cumarínicos/farmacologia , Triazóis/química , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/química , Cumarínicos/química , Hemólise/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Mol Cell Biochem ; 435(1-2): 193-196, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28501934

RESUMO

CX-4945 is a selective inhibitor of protein kinase CK2 exhibiting clinical significance. Its antitumor properties arise from the abrogation of CK2-mediated pro-survival cellular pathways. The presented data reveal the influence of CX-4945 on the growth of yeast cells showing variable potency against Saccharomyces cerevisiae deletion strains with different contents of CK2 subunits. The catalytic subunit CK2α appears to sensitize yeast to the CX-4945 action. Moreover, the compound suppresses hyphal growth and cell adhesion of Candida albicans, thereby abolishing some hallmarks of invasiveness of the pathogen. It is known that cancer patients are more prone to fungal infections. Our data unveil the dual-activity of CX-4945; when used in anti-cancer therapy, it may simultaneously prevent cancer-associated candidiasis.


Assuntos
Antifúngicos/farmacologia , Candida albicans/crescimento & desenvolvimento , Caseína Quinase II/antagonistas & inibidores , Naftiridinas/farmacologia , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Saccharomyces cerevisiae/crescimento & desenvolvimento , Fenazinas
20.
Yeast ; 34(6): 253-265, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28181315

RESUMO

Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) is a natural secondary plant product, originally isolated from the rhizomes of Rheum palmatum. Many reports show its diuretic, vasorelaxant, antibacterial, antiviral, anti-ulcerogenic, immunosuppressive, hepatoprotective, anti-inflammatory and anticancer potential. Emodin is a pleiotropic molecule capable of interacting with several major molecular targets, e.g. NF-κB, AKT/mTOR and STAT3. The compound can also act as an inhibitor of some protein kinases, with special affinity to protein kinase CK2. The aim of the presented report was to evaluate antifungal properties of emodin and its activity towards CK2 isolated from Candida cells. Our studies revealed that the compound suppressed growth of the cells of reference strains as well as clinical Candida strains, with minimal inhibitory concentration and minimal fungicidal concentration values between 12.5 and 200 µg/mL. Moreover, at a low concentration, the compound was able to effectively stop hyphal formation, thus showing a distinct antivirulent potential. Interestingly, we showed that emodin added to Candida culture inhibited the phosphorylation of many cellular proteins, presumably owing to the inhibition of protein kinase CK2. Notably, the enzyme isolated from the Candida cells was susceptible to emodin with IC50 of 2.8 µg/mL. Indeed, our computational modelling revealed that emodin was able to occupy the ATP-binding pocket of CK2. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Caseína Quinase II/antagonistas & inibidores , Emodina/farmacologia , Hifas/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Caseína Quinase II/isolamento & purificação , Hifas/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Microscopia de Fluorescência
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