RESUMO
Spilanthol is a bioactive alkylamide from the native Amazon plant species, Acmella oleracea. However, antifungal activities of spilanthol and its application to the therapeutic treatment of candidiasis remain to be explored. This study sought to evaluate the in vitro and in vivo antifungal activity of spilanthol previously isolated from A. oleracea (spilanthol(AcO)) against Candida albicans ATCC® 10231™, a multidrug-resistant fungal strain. Microdilution methods were used to determine inhibitory and fungicidal concentrations of spilanthol(AcO). In planktonic cultures, the fungal growth kinetics, yeast cell metabolic activity, cell membrane permeability and cell wall integrity were investigated. The effect of spilanthol(AcO) on the proliferation and adhesion of fungal biofilms was evaluated by whole slide imaging and scanning electron microscopy. The biochemical composition of the biofilm matrix was also analyzed. In parallel, spilanthol(AcO) was tested in vivo in an experimental vulvovaginal candidiasis model. Our in vitro analyses in C. albicans planktonic cultures detected a significant inhibitory effect of spilanthol(AcO), which affects both yeast cell membrane and cell wall integrity, interfering with the fungus growth. C. albicans biofilm proliferation and adhesion, as well as, carbohydrates and DNA in biofilm matrix were reduced after spilanthol(AcO) treatment. Moreover, infected rats treated with spilanthol(AcO) showed consistent reduction of both fungal burden and inflammatory processes compared to the untreated animals. Altogether, our findings demonstrated that spilanthol(AcO) is an bioactive compound against planktonic and biofilm forms of a multidrug resistant C. albicans strain. Furthermore, spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans. LAY SUMMARY: This study sought to evaluate the antifungal activity of spilanthol against Candida albicans ATCC® 10 231™, a multidrug-resistant fungal strain. Our findings demonstrated that spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans.
Assuntos
Candidíase Vulvovaginal , Doenças dos Roedores , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Biofilmes , Candida albicans , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/veterinária , Testes de Sensibilidade Microbiana/veterinária , Alcamidas Poli-Insaturadas/farmacologia , Ratos , Doenças dos Roedores/tratamento farmacológicoRESUMO
BACKGROUND: Microbial infections is a global public health problem. The aim of this work was to synthesize and evaluate the antimicrobial activity of novel triazoles, morpholines and thiosemicarbazones. METHODS: Compounds were synthesized using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. The antimicrobial activity of these compounds against bacteria and yeast was evaluated by the broth microdilution method. RESULTS: The proposed route for synthesis gave high to moderate yields, moreover these compounds were successfully characterized by 1H NMR, 13C NMR and LC-MS. Antimicrobial testing indicated that the thiosemicarbazone and morphine derivatives had the best antimicrobial activity against the microorganisms tested with minimum inhibitory concentrations (MIC) between 0.29 and 5.30 µM. Thiosemicarbazone derivative (12) was able to inhibit the growth of C. tropicalis, with minimum fungicidal concentration (MFC) of 0.55 µM. In addition, this compound was active against E. coli, S. aureus and S. epidermidis, with MIC values ranging from 0.29 to 1.11 µM. Moreover, the morpholine derivative (15) had an MIC value of 0.83 µM against C. albicans and E. coli. CONCLUSION: We have efficiently synthesized a series of eleven novel triazoles, thiosemicarbazones and morpholine derivatives using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. Thiosemicarbazone derivative (12) showed promising antifungal and antibacterial activity and these findings suggest that this compound can be used as scaffolds to design new antimicrobial drugs.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Morfolinas/farmacologia , Tiossemicarbazonas/farmacologia , Triazóis/farmacologia , Acetofenonas/síntese química , Acetofenonas/farmacologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/síntese química , Antifúngicos/síntese química , Candida/efeitos dos fármacos , Chalconas/síntese química , Chalconas/farmacologia , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Morfolinas/síntese química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Tiossemicarbazonas/síntese química , Triazóis/síntese químicaAssuntos
Toxidermias/etiologia , Imunossupressores/efeitos adversos , Tacrolimo/efeitos adversos , Adulto , Braço , Axila , Nádegas , Virilha , Humanos , Masculino , Pescoço , Coxa da PernaRESUMO
Vulvovaginal candidiasis (VVC) affects millions of women around the world every year. Candida albicans is the most frequently isolated pathogen in women and its rapid ability to develop resistance to first and second line therapies has boosted the search for new and effective antifungal agents. In this study, we show the in vitro anti-Candida activity of fifteen synthetic chalcone analogs and their antifungal potential in an in vivo model of VVC. Chalcone 12 showed potent antifungal effects, being able to inhibit the growth of Candida spp. at a concentration of 15.6 µg mL-1. In addition, mechanism of action studies have indicated the ergosterol fungal membrane as the target of this compound. Despite a considerable antifungal activity, the chalcone 12 showed high cytotoxicity in kidney cells lineages. Moreover, this compound was able to reduce Candida-associated virulence, impairing yeast-hyphal transition in C. albicans. An in vivo model of VVC showed that chalcone 12 significantly reduces the fungal load. Taken together, these findings showed that the chalcone 12 is a potent anti-Candida agent in vitro beyond of contribute to improve the fungal infection in a model of CVV. However, it showed low selectivity and high toxicity, suggesting molecular modifications to minimize these proprieties.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase Vulvovaginal/tratamento farmacológico , Chalconas/síntese química , Chalconas/farmacologia , Desenho de Fármacos , Animais , Antifúngicos/síntese química , Candida albicans/isolamento & purificação , Linhagem Celular , Chlorocebus aethiops , Cricetinae , Feminino , Humanos , Testes de Sensibilidade Microbiana , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Células VeroRESUMO
Leprosy is an important cause of disability in the developing world. Early diagnosis is essential to allow for cure and to interrupt transmission of this infection. MicroRNAs (miRNAs) are important factors for host-pathogen interaction and they have been identified as biomarkers for various infectious diseases. The expression profile of 377 microRNAs were analyzed by TaqMan low-density array (TLDA) in skin lesions of tuberculoid and lepromatous leprosy patients as well as skin specimens from healthy controls. In a second step, 16 microRNAs were selected for validation experiments with reverse transcription-quantitative PCR (qRT-PCR) in skin samples from new individuals. Principal-component analysis followed by logistic regression model and receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic potential of selected miRNAs. Four patterns of differential expression were identified in the TLDA experiment, suggesting a diagnostic potential of miRNAs in leprosy. After validation experiments, a combination of four miRNAs (miR-101, miR-196b, miR-27b, and miR-29c) was revealed as able to discriminate between healthy control and leprosy patients with 80% sensitivity and 91% specificity. This set of miRNAs was also able to discriminate between lepromatous and tuberculoid patients with a sensitivity of 83% and 80% specificity. In this work, it was possible to identify a set of miRNAs with good diagnostic potential for leprosy.
Assuntos
Marcadores Genéticos/genética , Hanseníase/diagnóstico , MicroRNAs/genética , Mycobacterium leprae/genética , Adulto , Diagnóstico Precoce , Humanos , Hanseníase/imunologia , Hanseníase/microbiologia , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Adulto JovemRESUMO
Leprosy is an important cause of disability in the developing world. Early diagnosis is essential to allow for cure and to interrupt transmission of this infection. MicroRNAs (miRNAs) are important factors for host-pathogen interaction and they have been identified as biomarkers for various infectious diseases. The expression profile of 377 microRNAs were analyzed by TaqMan low-density array (TLDA) in skin lesions of tuberculoid and lepromatous leprosy patients as well as skin specimens from healthy controls. In a second step, 16 microRNAs were selected for validation experiments with reverse transcription-quantitative PCR (qRT-PCR) in skin samples from new individuals. Principal-component analysis followed by logistic regression model and receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic potential of selected miRNAs. Four patterns of differential expression were identified in the TLDA experiment, suggesting a diagnostic potential of miRNAs in leprosy. After validation experiments, a combination of four miRNAs (miR-101, miR-196b, miR-27b, and miR-29c) was revealed as able to discriminate between healthy control and leprosy patients with 80% sensitivity and 91% specificity. This set of miRNAs was also able to discriminate between lepromatous and tuberculoid patients with a sensitivity of 83% and 80% specificity. In this work, it was possible to identify a set of miRNAs with good diagnostic potential for leprosy.
Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Marcadores Genéticos/genética , Curva ROC , Sensibilidade e Especificidade , MicroRNAs/genética , Diagnóstico Precoce , Reação em Cadeia da Polimerase em Tempo Real , Hanseníase/diagnóstico , Hanseníase/imunologia , Hanseníase/microbiologia , Mycobacterium leprae/genética , Mycobacterium leprae/imunologiaRESUMO
Hepatic involvement in a lepromatous leprosy (LL) patient is reported. The serum concentrations of aminotransferases were much higher than previously described in the leprosy literature. Other causes for hepatic damage were ruled out. Such hepatic involvement and elevation of aminotransferases have never been described in leprosy.