Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
Mais filtros











Intervalo de ano de publicação
1.
Int Microbiol ; 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39126447

RESUMO

Around 1.5 million mortality cases due to fungal infection are reported annually, posing a massive threat to global health. However, the effectiveness of current antifungal therapies in the treatment of invasive fungal infections is limited. Repurposing existing antifungal drugs is an advisable alternative approach for enhancing their effectiveness. This study evaluated the antifungal efficacy of the antiviral drug vidarabine against Candida albicans ATCC 90028. Antifungal susceptibility testing was performed by microbroth dilution assay and further processed to find the minimum fungicidal concentration. Investigation on probable mode of vidarabine action against C. albicans was assessed by using the ergosterol reduction assay, reactive oxygen species (ROS) accumulation, nuclear condensation, and apoptosis assay. Results revealed that C. albicans was susceptible to vidarabine action and exhibited minimum inhibitory concentration at 150 µg/ml. At a concentration of 300 µg/ml, vidarabine had fungicidal activity against C. albicans. 300 µg/ml vidarabine-treated C. albicans cells demonstrated 91% reduced ergosterol content. Annexin/FITC/PI assay showed that vidarabine (150 µg/ml) had increased late apoptotic cells up to 31%. As per the fractional inhibitory concentration index, vidarabine had synergistic activity with fluconazole and caspofungin against this fungus. The mechanism underlying fungicidal action of vidarabine was evaluated at the intracellular level, and probably because of increased nuclear condensation, enhanced ROS generation, and cell cycle arrest. In conclusion, this data is the first to report that vidarabine has potential to be used as a repurposed antifungal agent alone or in combination with standard antifungal drugs, and could be a quick and safe addition to existing therapies for treating fungal infections.

2.
Braz J Microbiol ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789908

RESUMO

Candida albicans is a polymorphic human fungal pathogen and the prime etiological agent responsible for candidiasis. The main two aspects of C. albicans virulence that have been suggested are yeast-to-hyphal (Y-H) morphological transitions and biofilm development. Anti-fungal agents targeting these virulence attributes enhances the antifungal drug development process. Repositioning with other non-fungal drugs offered a one of the new strategies and a potential alternative option to counter the urgent need for antifungal drug development. In the current study, an antiviral drug ganciclovir was screened as an antifungal agent against ATCC 90028, 10231 and clinical isolate (C1). Ganciclovir at 0.5 mg/ml concentration reduced 50% hyphal development on a silicon-based urinary catheter and was visualized using scanning electron microscopy. Ganciclovir reduced ergosterol biosynthesis in both strains and C1 isolate of C. albicans in a concentration-dependent manner. Additionally, a gene expression profile study showed that ganciclovir treatment resulted in upregulation of hyphal-specific repressors MIG1, TUP1, and NRG1 in C. albicans. Additionally, an in vivo study on the Bombyx mori silkworm model further evidenced the virulence inhibitory ability of ganciclovir (0.5 mg/ml) against C. albicans. This is the first report that explore the novel anti-morphogenic activities of ganciclovir against the pathogenic C. albicans strains, along with clinical isolates. Further, ganciclovir may be considered for therapeutic purpose after combinations with standard antifungal agents.

3.
Med Mycol ; 59(4): 366-378, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32658959

RESUMO

Candida albicans is a member of pathogens with potential drug resistance threat that needs novel chemotherapeutic strategies. Considering the multifarious biological activities including bioenhancer activity, anti-Candida potential of piperine was evaluated against planktonic/biofilm and hyphal growth of C. albicans alone or in combination as a synergistic agent with fluconazole. Piperine inhibits planktonic growth at or less than 15 µg/ml, hyphae induction at 5 µg/ml concentration, and exhibits stage-dependent activity against biofilm growth of a fluconazole-resistant strain of C. albicans (ATCC10231). Though piperine couldn't kill inoculum completely at minimum inhibitory concentration (MIC), it is fungicidal at higher concentrations, as shown in apoptosis assay. FIC index values indicate that piperine exhibits excellent synergistic activity with fluconazole against planktonic (0.123) and biofilm (0.215) growth of an FLC resistant strain. Mode of anti-Candida activity was studied by identifying piperine responsive proteins wherein the abundance of 25 proteins involved in stress response, signal transduction and cell cycle were modulated (22 up and 3 down-regulated) significantly in response to piperine (MIC50). Modulation of the proteins involved suggests that piperine affects membrane integrity leading to oxidative stress followed by cell cycle arrest and apoptosis in C. albicans. Flow cytometry-based mitochondrial membrane potential (MMP), cell cycle and apoptosis assay, as well as real-time quantitative polymerase chain reaction analysis of selected genes, confirms piperine induced oxidative stress (TRR1), cell cycle arrest and apoptosis (CaMCA1). Based on our results, we conclude that piperine inhibits planktonic and difficult-to treat-biofilm growth of C. albicans by affecting membrane integrity thereby inducing oxidative stress and apoptosis. LAY ABSTRACT: Piperine inhibit Candida albicans growth (planktonic and biofilm) significantly in our study. Piperine exhibits excellent synergistic potential with fluconazole The proteome analysis suggests that piperine induced membrane damage leads to oxidative stress followed by cell cycle arrest and apoptosis.


Assuntos
Alcaloides/farmacologia , Antifúngicos/farmacologia , Apoptose/efeitos dos fármacos , Benzodioxóis/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Hifas/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Biofilmes/crescimento & desenvolvimento , Candidíase/tratamento farmacológico , Farmacorresistência Fúngica , Sinergismo Farmacológico , Fluconazol/farmacologia , Hifas/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia
4.
Assay Drug Dev Technol ; 14(10): 567-572, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27982704

RESUMO

Tramadol is a synthetic, centrally acting low-affinity agonist of µ-opioid receptors in humans. It is used as an analgesic and is shown to have local anesthetic action. In this study, we have tried to explore its anti-Candida potential. Minimum inhibitory concentration (MIC50) and minimum fungicidal concentration (MFC) values were established. MIC50 ranged from 2 to 4 mg/mL, whereas MFC was recorded at 8 mg/mL. Also, the effect of tramadol on germ tube formation, adhesion, and biofilms in Candida albicans was studied. Tramadol impaired in vitro growth of C. albicans. A time-dependent killing assay showed that it kills C. albicans within 24 h of exposure. Tramadol has strong activity against Candida virulence factors such as yeast-to-hyphal form switching and adhesion. C. albicans biofilms, which are notoriously resistant to many antifungals, were sensitive to tramadol. At 8 mg/mL of tramadol, 82% of early stage biofilms and 52.88% of matured biofilms were inhibited. Although our results show that the antifungal effect of tramadol requires concentrations that can be achieved only locally, they may provide potential candidates for development of novel antifungal drugs.


Assuntos
Analgésicos Opioides/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Morfogênese/efeitos dos fármacos , Tramadol/farmacologia , Antifúngicos/farmacologia , Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana/métodos , Morfogênese/fisiologia
5.
Assay Drug Dev Technol ; 13(6): 307-12, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26241210

RESUMO

Exploring the potential of existing drugs for their unknown properties may offer advantages over conventional drug development by saving time and money. Candida albicans, an important human opportunist, shares many genetic properties with humans. This has encouraged us to study drugs that are not originally antifungals against C. albicans. In the present study, we have tested six antiepileptic drugs for their activities against C. albicans. Their effects on growth, time-dependent killing, yeast-to-hyphal form switching, and biofilms formation by C. albicans were studied. Out of the drugs studied, four drugs, which are γ-aminobutyric acid (GABA) receptor agonists in humans, inhibited growth, yeast-to-hyphal form switching, and biofilm formation in C. albicans. Lorazepam inhibited growth of C. albicans at 25 µg/ml, followed by midazolam and diazepam (minimum inhibitory concentrations 100 and 400 µg/ml, respectively). Members from other group voltage-gated sodium channel blockers failed to inhibit C. albicans. Our study has identified GABA receptor agonists used in epileptic therapy as potential candidates for antifungal drug development against the human pathogen C. albicans.


Assuntos
Anticonvulsivantes/farmacologia , Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candidíase/microbiologia , Agonistas GABAérgicos/farmacologia , Humanos , Hifas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia
6.
Funct Integr Genomics ; 15(1): 27-46, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25274312

RESUMO

The AP2/ERF family is one of the largest transcription factor gene families that are involved in various plant processes, especially in response to biotic and abiotic stresses. Complete genome sequences of one of the world's most important pulse crops chickpea (Cicer arietinum L.), has provided an important opportunity to identify and characterize genome-wide ERF genes. In this study, we identified 120 putative ERF genes from chickpea. The genomic organization of the chickpea ERF genes suggested that the gene family might have been expanded through the segmental duplications. The 120 member ERF family was classified into eleven distinct groups (I-X and VI-L). Transcriptional factor CarERF116, which is differentially expressed between drought tolerant and susceptible chickpea cultivar under terminal drought stress has been identified and functionally characterized. The CarERF116 encodes a putative protein of 241 amino acids and classified into group IX of ERF family. An in vitro CarERF116 protein-DNA binding assay demonstrated that CarERF116 protein specifically interacts with GCC box. We demonstrate that CarERF116 is capable of transactivation activity of and show that the functional transcriptional domain lies at the C-terminal region of the CarERF116. In transgenic Arabidopsis plants overexpressing CarERF116, significant up-regulation of several stress related genes were observed. These plants also exhibit resistance to osmotic stress and reduced sensitivity to ABA during seed germination. Based on these findings, we conclude that CarERF116 is an abiotic stress responsive gene, which plays an important role in stress tolerance. In addition, the present study leads to genome-wide identification and evolutionary analyses of chickpea ERF gene family, which will facilitate further research on this important group of genes and provides valuable resources for comparative genomics among the grain legumes.


Assuntos
Cicer/genética , Cicer/fisiologia , Genes de Plantas , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Fatores de Transcrição/metabolismo , Ácido Abscísico/farmacologia , Adaptação Fisiológica/genética , Sequência de Aminoácidos , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Sequência de Bases , Cromossomos de Plantas/genética , Secas , Congelamento , Duplicação Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Germinação/efeitos dos fármacos , Manitol/farmacologia , Modelos Moleculares , Dados de Sequência Molecular , Pressão Osmótica/efeitos dos fármacos , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Regiões Promotoras Genéticas/genética , Ligação Proteica , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Análise de Sequência de DNA , Estresse Fisiológico/efeitos dos fármacos , Transativadores/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/genética
7.
Phytomedicine ; 21(3): 268-76, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24200497

RESUMO

Acorus calamus (Sweet flag) has a long history of use and has numerous traditional and ethnomedicinal applications. Since ancient times, it has been used in various systems of medicines such as Ayurveda, Unani, Siddha, Chinese medicine, etc. for the treatment of various aliments like nervous disorders, appetite loss, bronchitis, chest pain, colic, cramps, diarrhea, digestive disorders, flatulence, gas, indigestion, rheumatism, sedative, cough, fever, bronchitis, inflammation, depression, tumors, hemorrhoids, skin diseases, numbness, general debility and vascular disorders. Various therapeutic potentials of this plant have been attributed to its rhizome. A number of active constituents from leaves, rhizomes and essential oils of A. calamus have been isolated and characterized. Of the constituents, alpha and beta-asarone are the predominant bioactive components. Various pharmacological activities of A. calamus rhizome such as sedative, CNS depressant, anticonvulsant, antispasmodic, cardiovascular, hypolipidemic, immunosuppressive, anti-inflammatory, cryoprotective, antioxidant, antidiarrheal, antimicrobial, anticancer and antidiabetic has been reported. Genotoxicity and mutagenecity of beta and alpha-asarone is reported, which limits their use at high dosage. Though A. calamus has been used since ancient times, many of its uses are yet to be scientifically validated. In the present review an attempt has been made to explore traditional uses and pharmacological properties of A. calamus.


Assuntos
Acorus/química , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Derivados de Alilbenzenos , Anisóis/efeitos adversos , Anisóis/farmacologia , Anisóis/uso terapêutico , Humanos , Medicina Tradicional , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Folhas de Planta , Rizoma
8.
Braz. j. microbiol ; 44(4): 1315-1320, Oct.-Dec. 2013. ilus, tab
Artigo em Inglês | LILACS | ID: lil-705294

RESUMO

In this study we report the potential of alcohols as morphogenetic regulators in Candida albicans. All the alcohols tested influenced various modes of growth like planktonic as well as biofilm forms. Viability was affected at high concentrations. Among the alcohols, the response of C. albicans to amyl alcohol (pentanol) was noteworthy. Amyl alcohol at a concentration 0.5% which was not inhibitory to growth and viability specifically inhibited morphogenetic switching from yeast to hyphal forms. It also inhibited normal biofilm development favoring yeast dominated biofilms. Based on this study we hypothesize that alcohols produced under anaerobic conditions may not favor biofilm development and support dissemination of yeast cells. Since anaerobic conditions are not found to favor production of quorum sensing molecules like farnesol, the alcohols may play a role in morphogenetic regulation.


Assuntos
Álcoois/metabolismo , Biofilmes/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Candida albicans/citologia , Candida albicans/crescimento & desenvolvimento , Viabilidade Microbiana/efeitos dos fármacos
9.
Braz. j. microbiol ; 44(3): 855-859, July-Sept. 2013. ilus, tab
Artigo em Inglês | LILACS | ID: lil-699817

RESUMO

Candida infections are very common in cancer patients and it is a common practice to prescribe antifungal antibiotics along with anticancer drugs. Yeast to hyphal form switching is considered to be important in invasive candidiasis. Targeting morphogenetic switching may be useful against invasive candidiasis. In this study, we report the antimorphogenetic properties of thirty cancer drugs.


Assuntos
Humanos , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Candida albicans/efeitos dos fármacos , Hifas/efeitos dos fármacos , Candida albicans/citologia , Candida albicans/crescimento & desenvolvimento , Reposicionamento de Medicamentos , Hifas/citologia , Hifas/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Microscopia
11.
Arch Oral Biol ; 58(9): 1109-15, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23722042

RESUMO

OBJECTIVES: Aliskiren, the first in a new class of orally active renin inhibitors, is licensed for the treatment of hypertension. It inhibits plasma renin activity directly, thereby reducing generation of angiotensin II. In this study, we have explored the anti-Candida properties of aliskiren. METHODS: Candida albicans was cultured in the presence or absence of aliskiren for various time periods. Subsequently, inhibition of growth, germtube formation, adhesion, early/matured biofilm development and secreted aspartic protease (SAP) activity were studied. RESULTS: When cultured in the presence of aliskiren, Candida showed significant reduction in the activity of aspartic proteases. Aliskiren impaired in vitro growth of C. albicans. It also affected two other virulence factors, germtube and adhesion. There is reduction in early and matured biofilm when treated with aliskiren. CONCLUSIONS: Aliskiren could be considered as a candidate for antifungal drug development.


Assuntos
Amidas/farmacologia , Antifúngicos/farmacologia , Anti-Hipertensivos/farmacologia , Ácido Aspártico Proteases/metabolismo , Candida albicans/efeitos dos fármacos , Fumaratos/farmacologia , Renina/antagonistas & inibidores , Amidas/química , Biofilmes/efeitos dos fármacos , Candida albicans/enzimologia , Candida albicans/crescimento & desenvolvimento , Técnicas de Cultura de Células , Reposicionamento de Medicamentos , Fumaratos/química , Microscopia Eletrônica de Varredura
12.
Springerplus ; 2(1): 26, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23449869

RESUMO

The aim of this work was to evaluate the anti-Candida efficacy of twenty five molecules of plant origin. Based on their MICs, effective molecules were categorized into four categories. Susceptibility testing of test compounds was carried out by standard methodology (M27-A2) as per CLSI guidelines. Minimum Fungicidal Concentration (MFC) was determined as the lowest concentration of drug killing 99.9% cells. Effect on sterol profile was evaluated by sterol quantitation method. Among the screened molecules, cinnamaldehyde, piperidine, citral, furfuraldehyde and indole were potent inhibitors of growth and viability. Exposure of Candida cells to cinnamaldehyde, piperidine, citral, furfuraldehyde, indole, α- and ß- pinene at MIC's, altered ergosterol profile. Our results indicate that the molecules altering sterol profile may exert their antifungal effect through inhibition of ergosterol biosynthesis and could be good candidates for fungal specific drug development.

13.
Braz J Microbiol ; 44(4): 1315-20, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24688528

RESUMO

In this study we report the potential of alcohols as morphogenetic regulators in Candida albicans. All the alcohols tested influenced various modes of growth like planktonic as well as biofilm forms. Viability was affected at high concentrations. Among the alcohols, the response of C. albicans to amyl alcohol (pentanol) was noteworthy. Amyl alcohol at a concentration 0.5% which was not inhibitory to growth and viability specifically inhibited morphogenetic switching from yeast to hyphal forms. It also inhibited normal biofilm development favoring yeast dominated biofilms. Based on this study we hypothesize that alcohols produced under anaerobic conditions may not favor biofilm development and support dissemination of yeast cells. Since anaerobic conditions are not found to favor production of quorum sensing molecules like farnesol, the alcohols may play a role in morphogenetic regulation.


Assuntos
Álcoois/metabolismo , Biofilmes/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Candida albicans/citologia , Candida albicans/crescimento & desenvolvimento , Viabilidade Microbiana/efeitos dos fármacos
14.
Biofouling ; 29(1): 87-96, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23216018

RESUMO

Biofilm-related infections caused by Candida albicans and associated drug resistant micro-organisms are serious problems for immunocompromised populations. Molecules which can prevent or remove biofilms are needed. Twenty-eight terpenoids of plant origin were analysed for their activity against growth, virulence attributes, and biofilms of C. albicans. Eighteen molecules exhibited minimum inhibitory concentrations of <2 mg ml(-1) for planktonic growth. Selected molecules inhibited yeast to hyphal dimorphism at low concentrations (0.031-0.5 mg ml(-1)), while adhesion to a solid surface was prevented at 0.5-2 mg ml(-1). Treatment with 14 terpenoids resulted in significant (p < 0.05) inhibition of biofilm formation, and of these, linalool, nerol, isopulegol, menthol, carvone, α-thujone, and farnesol exhibited biofilm-specific activity. Eight terpenoids were identified as inhibitors of mature biofilms. This study demonstrated the antibiofilm potential of terpenoids, which need to be further explored as therapeutic strategy against biofilm associated infections of C. albicans.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Óleos Voláteis/farmacologia , Terpenos/farmacologia , Anilidas/química , Antifúngicos/administração & dosagem , Candida albicans/crescimento & desenvolvimento , Candida albicans/patogenicidade , Adesão Celular/efeitos dos fármacos , Violeta Genciana/química , Hifas/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Hifas/patogenicidade , Hifas/fisiologia , Testes de Sensibilidade Microbiana , Óleos Voláteis/administração & dosagem , Terpenos/administração & dosagem , Sais de Tetrazólio/química , Virulência/efeitos dos fármacos
15.
Phytomedicine ; 20(2): 139-42, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23123225

RESUMO

Anti-Candida potential of Acorus calamus rhizome and its active principle, ß-asarone, was evaluated against the human fungal pathogen, Candida albicans. ß-Asarone exhibited promising growth inhibitory activity at 0.5mg/ml and it was fungicidal at 8 mg/ml. Time dependant kill curve assay showed that MFC of ß-asarone was highly toxic to C. albicans, killing 99.9% inoculum within 120 min of exposure. ß-Asarone caused significant inhibition of C. albicans morphogenesis and biofilm development at sub-inhibitory concentrations. Our data indicate that the growth inhibitory activity of ß-asarone might be through inhibition of ergosterol biosynthesis. Hemolytic assay showed that ß-asarone is non-toxic, even at concentrations approaching MIC value. Our results suggest that ß-asarone may be safe as a topical antifungal agent.


Assuntos
Acorus/química , Anisóis/farmacologia , Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Ergosterol/biossíntese , Rizoma/química , Derivados de Alilbenzenos , Candida albicans/efeitos dos fármacos , Candida albicans/metabolismo , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana
16.
Braz J Microbiol ; 44(3): 855-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24516452

RESUMO

Candida infections are very common in cancer patients and it is a common practice to prescribe antifungal antibiotics along with anticancer drugs. Yeast to hyphal form switching is considered to be important in invasive candidiasis. Targeting morphogenetic switching may be useful against invasive candidiasis. In this study, we report the antimorphogenetic properties of thirty cancer drugs.


Assuntos
Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Candida albicans/efeitos dos fármacos , Hifas/efeitos dos fármacos , Candida albicans/citologia , Candida albicans/crescimento & desenvolvimento , Reposicionamento de Medicamentos , Humanos , Hifas/citologia , Hifas/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Microscopia
17.
Chemotherapy ; 57(5): 372-80, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21997126

RESUMO

BACKGROUND: Anticancer/antineoplastic agents could be a good resource for the discovery of novel antifungal agents and targets since human beings share a common eukaryotic heritage with fungi. METHODS: Thirty commonly prescribed anticancer drugs belonging to 12 different classes were analyzed for their effects on the growth of Candida albicans. Minimum inhibitory concentrations (MICs) were obtained using standard CLSI-M27 A2 methodology, and minimal fungicidal concentrations (MFCs) were determined via the agar plate method. RESULTS: Anticancer agents inhibited the growth of C. albicans in a concentration-dependent manner. Nine drugs from different classes were effective at low concentrations (≤50 µg·ml(-1)), while 15 anticancer drugs exhibited MICs of 100 µg·ml(-1). Sixteen out of 30 drugs exerted fungicidal activity in the range of 400-800 µg·ml(-1). CONCLUSIONS: MICs and MFCs for 30 anticancer drugs were established against C. albicans. Our study highlighted the anti-Candida potential of these drugs, which may give insights to unexplored targets for antifungal chemotherapy.


Assuntos
Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Candida albicans/efeitos dos fármacos , Antifúngicos/classificação , Antineoplásicos/classificação , Candida albicans/fisiologia , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana
18.
Phytomedicine ; 18(13): 1181-90, 2011 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-21596542

RESUMO

Anti-Candida potential of six terpenoids were evaluated in this study against various isolates of Candida albicans (n=39) and non-C. albicans (n=9) that are differentially susceptible to fluconazole. All the six terpenoids tested, showed excellent activity and were equally effective against isolates of Candida sps., tested in this study. Linalool and citral were the most effective ones, inhibiting all the isolates at ≤0.064% (v/v). Five among the six terpenoids tested were fungicidal. Time dependent kill curve assay showed that MFCs of linalool and eugenol were highly toxic to C. albicans, killing 99.9% inoculum within seven min of exposure, while that of citronellal, linalyl acetate and citral required 15min, 1h and 2h, respectively. FIC index values (Linalool - 0.140, benzyl benzoate - 0.156, eugenol - 0.265, citral - 0.281 and 0.312 for linalyl acetate and citronellal) and isobologram obtained by checker board assay showed that all the six terpenoids tested exhibit excellent synergistic activity with fluconazole against a fluconazole resistant strain of C. albicans. Terpenoids tested arrested C. albicans cells at different phases of the cell cycle i.e. linalool and LA at G1, citral and citronellal at S phase and benzyl benzoate at G2-M phase and induced apoptosis. Linalool, citral, citronellal and benzyl benzoate caused more than 50% inhibition of germ tube induction at 0.008%, while eugenol and LA required 0.032 and 0.016% (v/v) concentrations, respectively. MICs of all the terpenoids for the C. albicans growth were non toxic to HeLa cells. Terpenoids tested exhibited excellent activity against C. albicans yeast and hyphal form growth at the concentrations that are non toxic to HeLa cells. Terpenoids tested in this study may find use in antifungal chemotherapy, not only as antifungal agents but also as synergistic agents along with conventional drugs like fluconazole.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Terpenos/farmacologia , Monoterpenos Acíclicos , Aldeídos/farmacologia , Apoptose/efeitos dos fármacos , Candidíase/tratamento farmacológico , Ciclo Celular/efeitos dos fármacos , Farmacorresistência Fúngica , Eugenol/farmacologia , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Monoterpenos/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química
19.
Mycoses ; 54(6): e697-703, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21605190

RESUMO

Regulation of morphogenesis through the production of chemical signalling molecules such as isoamyl alcohol, 2-phenylethyl alcohol, 1-dodecanol, E-nerolidol and farnesol is reported in Candida albicans. The present study focuses on the effect of ethyl alcohol on C. albicans dimorphism and biofilm development. Ethyl alcohol inhibited germ tube formation induced by the four standard inducers in a concentration-dependent manner. The germ tube inhibitory concentration (4%) did not have any effect on the growth and viability of C. albicans cells. Ethyl alcohol also inhibited the elongation of germ tubes. Four percentage of ethyl alcohol significantly inhibited biofilm development on polystyrene and silicone surfaces. We suggest a potential morphogenetic regulatory role for ethyl alcohol, which may influence dissemination, virulence and establishment of infection.


Assuntos
Candida albicans/citologia , Candida albicans/efeitos dos fármacos , Etanol/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Microbiologia Ambiental , Humanos , Viabilidade Microbiana/efeitos dos fármacos , Poliestirenos , Silício
20.
BMC Plant Biol ; 11: 70, 2011 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-21513527

RESUMO

BACKGROUND: Chickpea (Cicer arietinum L.) is an important grain-legume crop that is mainly grown in rainfed areas, where terminal drought is a major constraint to its productivity. We generated expressed sequence tags (ESTs) by suppression subtraction hybridization (SSH) to identify differentially expressed genes in drought-tolerant and -susceptible genotypes in chickpea. RESULTS: EST libraries were generated by SSH from root and shoot tissues of IC4958 (drought tolerant) and ICC 1882 (drought resistant) exposed to terminal drought conditions by the dry down method. SSH libraries were also constructed by using 2 sets of bulks prepared from the RNA of root tissues from selected recombinant inbred lines (RILs) (10 each) for the extreme high and low root biomass phenotype. A total of 3062 unigenes (638 contigs and 2424 singletons), 51.4% of which were novel in chickpea, were derived by cluster assembly and sequence alignment of 5949 ESTs. Only 2185 (71%) unigenes showed significant BLASTX similarity (<1E-06) in the NCBI non-redundant (nr) database. Gene ontology functional classification terms (BLASTX results and GO term), were retrieved for 2006 (92.0%) sequences, and 656 sequences were further annotated with 812 Enzyme Commission (EC) codes and were mapped to 108 different KEGG pathways. In addition, expression status of 830 unigenes in response to terminal drought stress was evaluated using macro-array (dot blots). The expression of few selected genes was validated by northern blotting and quantitative real-time PCR assay. CONCLUSION: Our study compares not only genes that are up- and down-regulated in a drought-tolerant genotype under terminal drought stress and a drought susceptible genotype but also between the bulks of the selected RILs exhibiting extreme phenotypes. More than 50% of the genes identified have been shown to be associated with drought stress in chickpea for the first time. This study not only serves as resource for marker discovery, but can provide a better insight into the selection of candidate genes (both up- and downregulated) associated with drought tolerance. These results can be used to identify suitable targets for manipulating the drought-tolerance trait in chickpea.


Assuntos
Adaptação Fisiológica , Cicer/genética , Secas , Etiquetas de Sequências Expressas , Estresse Fisiológico , Biomassa , Cicer/fisiologia , Dessecação , Regulação da Expressão Gênica de Plantas , Biblioteca Gênica , Genes de Plantas , Genótipo , Hibridização Genética , Família Multigênica , Fenótipo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Brotos de Planta/genética , Brotos de Planta/metabolismo , Alinhamento de Sequência , Água/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA