In vitro antifungal activity of organic compounds derived from amino alcohols against onychomycosis

Abstract Onychomycosis is a fungal infection of the nail caused by high densities of filamentous fungi and yeasts. Treatment for this illness is long-term, and recurrences are frequently detected. This study evaluated in vitro antifungal activities of 12 organic compounds derived from amino alcohols against standard fungal strains, such as Trichophyton rubrum CCT 5507 URM 1666, Trichophyton mentagrophytes ATCC 11481, and Candida albicans ATCC 10231. The antifungal compounds were synthesized from p-hydroxybenzaldehyde (4a-4f) and p-hydroxybenzoic acid (9a-9f). Minimum inhibitory concentrations and minimum fungicidal concentrations were determined according to Clinical and Laboratory Standards Institute protocols M38-A2, M27-A3, and M27-S4. The amine series 4b-4e, mainly 4c and 4e compounds, were effective against filamentous fungi and yeast (MIC from 7.8 to 312 µg/mL). On the other hand, the amide series (9a-9f) did not present inhibitory effect against fungi, except amide 9c, which demonstrated activity only against C. albicans. This allowed us to infer that the presence of amine group and intermediate carbon number (8C-11C) in its aliphatic side chain seems to be important for antifungal activity. Although these compounds present cytotoxic activity on macrophages J774, our results suggest that these aromatic compounds might constitute potential as leader molecules in the development of more effective and less toxic analogs that could have considerable implications for future therapies of onychomycosis.

Factors impacting the growth and nutritional status of cystic fibrosis patients younger than 10 years of age who did not undergo neonatal screening / Fatores que afetam o crescimento e estado nutricional de pacientes com fibrose cística com idade inferior a 10 anos e que não foram submetidos à triagem neonatal

OBJECTIVE: The aim of this study was to evaluate by clinical and laboratory parameters how cystic fibrosis (CF) affects growth and nutritional status of children who were undergoing CF treatment but did not receive newborn screening. METHODS: A historical cohort study of 52 CF patients younger than 10 years of age were followed in a reference center in Campinas, Southeast Brazil. Anthropometric measurements were abstracted from medical records until March/2010, when neonatal screening program was implemented. Between September/2009 and March/2010, parental height of the 52 CF patients were also measured. RESULTS: Regarding nutritional status, four patients had Z-scores ≤-2 for height/age (H/A) and body mass index/age (BMI/A). The following variables were associated with improved H/A ratio: fewer hospitalizations, longer time from first appointment to diagnosis, longer time from birth to diagnosis and later onset of respiratory disease. Forced vital capacity [FVC(%)], forced expiratory flow between 25-75% of FVC [FEF25-75(%)], forced expiratory volume in the first second [FEV1(%)], gestational age, birth weight and early respiratory symptoms were associated with improved BMI/A. CONCLUSIONS: Greater number of hospitalizations, diagnosis delay and early onset of respiratory disease had a negative impact on growth. Lower spirometric values, lower gestational age, lower birth weight, and early onset of respiratory symptoms had negative impact on nutritional status. Malnutrition was observed in 7.7% of cases, but 23% of children had nutritional risk. .

OBJETIVO: Avaliar por meio de parâmetros clínicos e laboratoriais como a fibrose cística (FC) afeta o crescimento e estado nutricional de crianças submetidas ao tratamento de FC que não foram submetidas à triagem neonatal. MÉTODOS: Uma coorte histórica com 52 pacientes com FC menores de 10 anos foi acompanhada em um centro de referência em Campinas, Sudeste do Brasil. Peso e altura foram coletados de prontuários médicos até março de 2010, quando a triagem neonatal foi implementada. Entre setembro de 2009 a março de 2010 a altura dos pais foi medida. RESULTADOS: Quatro pacientes tiveram escores Z ≤ -2 para altura/idade (A/I) e índice de massa corporal/idade (IMC/A). As seguintes variáveis foram associadas com melhor razão A/I: menor número de hospitalizações, maior tempo entre a primeira consulta e o diagnóstico, maior tempo entre o nascimento e o diagnóstico e início tardio da doença respiratória. Capacidade vital forçada [CVF(%)], fluxo expiratório forçado entre 25-75% da CVF [FEF25-75(%)], volume expiratório forçado no primeiro segundo [VEF1(%)], idade gestacional, peso ao nascer e início dos sintomas respiratórios foram associados com melhor IMC/I. CONCLUSÕES: Maior número de hospitalizações, retardo no diagnóstico e início precoce da doença respiratória tiveram impacto negativo no crescimento. Menores valores espirométricos, menor idade gestacional, menor peso ao nascer e o início precoce dos sintomas respiratórios tiveram impacto negativo no estado nutricional. A desnutrição foi observada em 7,7% dos casos, mas 23% das crianças apresentaram risco nutricional. .

Estudo comparativo da susceptibilidade de isolados clínicos de Cryptococcus neoformans (Sanfelice, 1895) frente a alguns antifúngicos de uso hospitalar e extratos vegetais obtidos de plantas medicinais da região semiárida sergipana / Comparative study of the susceptibility of clinical isolates of Cryptococcus neoformans (Sanfelice) against some antifungal agents of hospital use and plant extracts obtained from medicinal plants of the semiarid Sergipe region, Brazil

O uso de plantas medicinais no combate as micoses é uma prática comum nas comunidades rurais e, neste contexto, o objetivo desse trabalho foi analisar o perfil de sensibilidade de isolados clínicos de C. neoformans frente a extratos brutos aquosos e antifúngicos de uso hospitalar utilizando a técnica de difusão em disco. Esses produtos naturais foram obtidos de plantas medicinais popularmente utilizadas por comunidades do sertão sergipano. Foram analisados os extratos brutos aquosos de juazeiro (Ziziphus joazeiro Mart.), catingueira (Caesalpinia pyramidalis Tul.), quixabeira (Bumelia sartorum Mart.) e jatobá (Hymenaea courbaril L.). Do juazeiro foi testado o extrato preparado a partir do infuso da entrecasca e da decocção da folha. Da catingueira foi utilizado o extrato preparado a partir do infuso das folhas. Da quixabeira o extrato utilizado foi preparado a partir da decocção da entrecasca e do jatobá maceração da entrecasca. Todos esses produtos naturais foram submetidos aos seguintes tratamentos: exposição ou não a luz ultravioleta e autoclavagem (121ºC por 10minutos). Em paralelo as leveduras patogênicas foram testadas frente aos seguintes antifúngicos de uso hospitalar: anfotericina B, fluconazol, Itraconazol, Miconazol e cetoconazol. Todos os extratos brutos aquosos apresentaram ação antifúngica frente a todas as linhagens clínicas de Cryptococcus neoformans. O tratamento de submeter à autoclavagem e exposição à luz ultravioleta apresentaram melhores resultados de ação antifúngica. Sendo que o tratamento de autoclavar o extrato bruto aquoso prevaleceu estatisticamente com os melhores resultados. Outros estudos de atividade antimicrobiano são necessários para corroborar a ação antimicótica dos produtos natuais testados, como pro exemplo killer-time e fracionamento do teste de micodiluição. No teste de sensibilidade dos antifúngicos realizado foi demonstrado que as leveduras apresentaram resistência preocupante ao fluconazol e a itraconazol pelo método de difusão em disco. Para novos conhecimentos desse perfil de resistência há necessidade de testes de melhor acurácia, como por exemplo, microdiluição. Para tanto, deve-se padronizar os testes de sensibilidade quando há uso de produtos naturais oriundos de plantas medicinais, além de fornecer alternativas de uso aos pacientes cometidos por essa levedura com fornecimento de dados científicos que comprovem a ação dos produtos naturais e plantas medicinais de largo uso no sertão sergipano.

The use of medicinal plants to combat mycoses is a common practice in rural communities, and, in this context, the aim of this study was to analyze the sensitivity of clinical isolates of C. neoformans in relation to aqueous crude extracts and antifungal agents of hospital use using the disc diffusion technique. These natural products were obtained from medicinal plants popularly used empirically by backland communities in Sergipe, Brazil. The aqueous crude extracts of Ziziphus joazeiro Mart., Caesalpinia pyramidalis Tul., Bumelia sartorum Mart. and Hymenaea courbaril L. were analyzed. From the Ziziphus joazeiro Mart., we tested the extract prepared from the infusion of the inner bark and the decoction of the leaf. From the Caesalpinia pyramidalis Tul., the extract used was prepared from the infusion of the leaves. From Bumelia sartorum Mart., the extract used was prepared from the decoction of the bark, and from the Hymenaea courbaril L. we prepared the extract from the maceration of the inner bark. All these natural products were subjected to the following treatments: exposure to ultraviolet light or not and autoclaving (121°C for 10minutes). Amphotericin B, fluconazole, itraconazole, miconazole and ketoconazole were tested. All aqueous crude extracts showed antifungal activity against all clinical strains of Cryptococcus neoformans. The treatment that underwent autoclaving and exposure to ultraviolet light showed better results for antifungal action. The treatment with autoclaving of the aqueous crude extract statistically prevailed with the best results. There is the need to perform some treatments using these natural products based on the tested medicinal plants for better antifungal activity against this pathogenic yeast so they become more effective. In the antifungal susceptibility test performed, it was demonstrated that the yeast had worrying resistance to fluconazole and itraconazole by the disc diffusion method. FOr further knowledge on this resistance profile, there is the need of tests with greater accuracy, such as the microdilution test. To do so, susceptibility testing must be standardized when there is the use of natural products derived from medicinal plants, in addition to the provision of alternative uses by patients affected by this yeast, providing scientific data demonstrating the use and action of the natural products and medicinal plants of wide use in Sergipe, Brazil.

Synthesis, DNA cleavage and antimicrobial activity of 4-thiazolidinones-benzothiazole conjugates.

Antimicrobial screening of several novel 4-thiazolidinones with benzothiazole moiety has been performed. These compounds were evaluated for antimicrobial activity against a panel of bacterial and fungal strains. The strains were treated with these benzothiazole derivatives at varying concentrations, and MIC’s were calculated. Structures of these compounds have been determined by spectroscopic studies viz., FT-IR, 1H NMR, 13C NMR and elemental analysis. Significant antimicrobial activity was observed for some members of the series, and compounds viz. 3-(4-(benzo[d]thiazol-2-yl) phenyl)-2-(4-methoxyphenyl)thiazolidin-4-one and 3-(4-(benzo[d]thiazol-2-yl)phenyl)-2-(4-hydroxy phenyl)thiazolidin-4-one were found to be the most active against E.coli and C.albicans with MIC values in the range of 15.6–125 μg/ml. Preliminary study of the structure–activity relationship revealed that electron donating groups associated with thiazolidine bearing benzothiazole rings had a great effect on the antimicrobial activity of these compounds and contributes positively for the action. DNA cleavage experiments gave valuable hints with supporting evidence for describing the mechanism of action and hence showed a good correlation between their calculated MIC’s and its lethality.

Antifungal activity of the ethanolic extracts of Punica granatum L. and evaluation of the morphological and structural modifications of its compounds upon the cells of Candida spp.

Ethanolic crude extracts prepared from the arils and seeds, pericarp, peels and from the whole fruit of Punica granatum, known as pomegranate, had their antifungal activity tested against Candida spp. The ethanolic crude extracts were analyzed by Mass Spectrometry and yielded many compounds such as punicalagin and galladydilacton. The extracts from the pericarp and peel showed activity against Candida spp., with MICs of 125 µg/mL. The effect of pericarp and peel extracts upon the morphological and structure of C. albicans and C. krusei were examined by scanning and transmission electron microscopy, with the visualization of an irregular membrane and hyphae, formation of vacuoles and thickening of the cell wall. The data obtained revealed potential antimicrobial activity against yeasts cells of the Candida genus, and the bioactive compounds could be responsible for changes in cell morphology and structure. The data obtained open new perspectives for future research in continuation to this study, where information such as determination of the site of action of the compounds could contribute to an alternative therapy against these organisms.

Antifungal activity of essential oil and alcoholic extract of carum copticum against fluconazole-resistant and susceptible candida albicans isolated

Ajowan is an annual herbaceous essential oil of Carum copticom. The main components of the oil are Tymol, beta-pinene, gamma- terpinene and Sabinene. The fruit oil of Carum copticum has been reported to have several therapeutic effects including anti fungal, anti bacterial and anti viral, … Candida albicans is an opportunistic fungus and transforms into pathogenic form in favorable conditions, causing fungal diseases. In this study essential oil and alcoholic extract of Carum copticum were gained and Microdilution Broth method were used for detection of minimum inhibition concentration [MIC] and minimum fungicide concentration [MFC] of 11 clinical isolates of Candida albicans and Standard strain [PTCC50-27]. Results show that MIC for essential oil is 0.43 micro g/ml, 0.87 micro g/ml and for alcoholic extract is 3.51 micro g/ml, 7.03 micro g/ml, 1/75 micro g/ml. Thus, it seems that Carum copticum could inhibit Candida albicans growth by a similar mechanism which occurs by Fluconazole [FLZ]. In general, the results obtained in this study indicate that Carum copticum has potential values for growth inhibition of Candida albicans in vitro. In recent years, systemic fungal infections due to Candida species have been received major consideration about inducing mortality in nosocomial patients because of increasing in immunocompromised disorders such as AIDS and hematological disorders as well as long term use of broad spectrum antibiotics and corticosteroids. The present study was done with the aim of evaluating antifungal effects of essential oil and alcoholic extract from Carum copticum against Fluconazole [FLZ] susceptible and Fluconazole resistance Candida albicans strains isolated from different types of Candidiasis. Standard drug susceptibility tests with broth dilution technique were used to measure the in vitro antifungal activity of essential oil and alcoholic extract from Carum copticum. According to our results, it seems that Carum copticum could inhibit Candida albicans growth by a similar mechanism which occurs by FLZ and could be used as a potential antifungal agent especially with FLZ

Actividad antifúngica de quitosano carbamato de etilo en Candida albicans / Antifungal activity of chitosano ethil carbamate on Candida albicans

El incremento de las infecciones producidas en seres humanos y/o animales por hongos y el aumento de la resistencia de estos últimos a algunos farmacos, han conducido a la búsqueda de nuevos productos con actividad antifúngica. Producto de la síntesis química se ha obtenido la sustancia de origen natural, llamada Quitosano Carbamato de etilo (QCE) que ha demostrado acción antifúngica, particularmente a Candida albicans. Los objetivos de este trabajo fueron determinar ¶in vitro la Concentración Mínima Inhibitoria (CIM), Concentración Letal Media (CLM) y Letal (CL) de QCE para cultivos de C. albicans en CM al 2 por ciento. Establecer para esta misma levadura su curva de crecimiento, el tiempo de inicio de acción del QCE y los cambios morfoló-gicos de las celulas levaduriformes en CM al 2 por ciento con adición de QCE (0.89 mg/mL). Ademßs, determinar la acción del QCE (0.89 mg/mL) para las levaduras Criptococcus albus, Saccharomyces cerevisiae, Sporobolomyces roseus y 5 cepas de C. albicans aisladas de casos clínicos en el Hospital Clínico Regional Valdivia (H.C.R.V.). La CIM fue 0.25 mg/mL, la CLM fue 0.45 mg/mL y la CL 0,89 mg/mL. La curva de crecimiento elaborada para los cultivos de C. albicans sin adición de QCE fue la típica de una levadura y, por el contrario, la elaborada para los cultivos adicionados con QCE sólo registró la etapa de latencia. El tiempo de inicio de la acción del QCE para la cepa control de C. albicans comienza a las 12 horas de incubación. Las celulas de C. albicans obtenidas de cultivos tratados con QCE se mostraron colapsadas, de menor tamaño, no forman tubo germinativo y tampoco pseudomicelio. El QCE inhibió el desarrollo de cultivos de C. albus, S. cerevisiae, S. roseus y para tres de cinco cepas ensayadas de C. albicans obtenidas desde casos clínicos.

Sensibilidad de hongos miceliares dematiaceos a diez antifungicos empleando un metodo de difusion en agar / In vitro susceptibiblity of dematiaceous fungi to ten antifungal drugs using an agar difussion test

Se ha evaluado la utilidad del metodo de difusion en agar NeoSensitabs para determinar la sensibilidad in vitro de 52 aislamientos de hongos filamentosos dematiaceos a diez antifungicos: anfotericina B.5-fluorocitosina, Ketoconasol, fluconazol, itraconazol, terbinafina, bifonazol, miconazol, clotrimazol, y griseofulvina. Para la preparacion del inoculo se ultilizo un metodo espectrofotometrico empleandose los medios de Shadomy y Casitone agar (CAS), simultaneamente. Todos los aislamientos fueron sensibles, al itraconazol, terbinafina y bifonazol. Al ketonazol el 90,4% resultaron sensibles al miconazol el 71% y al clotrimazol el 46%. El 63% de las cepas fueron sensibles a la anfotericina B y el 28,8% resistente. Por el contrario, el 94,2% de los aislamientos resultaron resistentes a la griseofulvina y el 96% al flucanazol. El 100% de las cepas fueron resistentes a la 5-fluorocitosina. Las zonas de inhibicion no mostraron variaciones en cuanto a la sensibilidad dependiendo del medio; sin embargo, hubo un mejor desarrollo fungico en el medio CAS. Las variaciones en la sensibiblidad observadas con especies como Exophiala spinifera y Fonsecaea pedrosi justificarian el estudio de la sensibiblidad in vitro para valorar el tratamiento clinico con antifungicos. Estos resultados demuestran que el metodo de difusion en agar NeoSensitabs es facil de realizar, rapido y economico por lo que esta al alcance de muchos laboratorios clinicos para el estudio de la sensibilidad in vitro en mochos dematiaceos

Antifungal activity of bicyclic heterocyclic-1,2-diazole.

A novel series of heterocyclic-1,2 diazole namely N1-iso nicotinoyl-5,5'-dimethyl cyclohexane-4-(sulpha/substituted phenylazo)-1,2-diazoles have been synthesized. The compounds were screened for the anti-fungal properties against building fungi. The fungal species used for this purpose were Aspergillus niger and Pencillium frequentans. It was found that out of a series of 25 compounds, fourteen have shown significant fungicidal properties against both the above species. Minimum inhibition concentration was observed between 100 and 200 ppm for most of the compounds.

Synthesis of new pyrroles and their biological activities.

Coumarino acid hydrazides and acid hydrazide of 2-oxy 3, 5, 6-trichloropyridine were prepared in two steps. These acid hydrazides on condensation with Acetonyl acetone i.e. 2,5-hexanedione yields new pyrroles. These pyrroles showed good to moderate antimicrobial activities against Alternaria brassicicola, Aspergillus niger, E. coli and Lactobacillus.

Synthesis of new (4-alkylamino-4'-fluoro)-diphenyl sulphones with potential biological activity

In the present work, we report the synthesis and characterization of five (4-alkylalmino-4'-fluoro)-diphenyl sulphones, four of which have not been described before. In a preliminary evaluation of their biological activity, these products showed no effect on several Gram-positive and Gram-negative bacteria and yeasts.

Synthesis of some novel peryhdrotriazepine-3,6-diones of potential antifungal activity

Several derivatives of perhydro-1,2,5-triazapine-3,6-diones, such as the 1-substituted carbonyl, 1-substituted aminomethylcarbonyl, 1-substituted thiocarbamoyl and 4,7-diarylidene derivatives, were prepared and in vitro tested for their antifungal activity

Synthesis of some phenoxymethylbenzimidazole derivatives as potential antibacterial and antifungal agents

Certain new phenoxymethylbenzimidazole derivatives were prepared and evaluated for antibacterial and antifungal activities

Synthesis and evaluation for antibacterial and antifungal activities of new triazolothiadiazole and triazolothiadiazine derivatives

Novel series of fused hetercycles, namely; 6-substituted-3-[2-phenylquinol-4-yl]-1, 2, 4-triazolo [3, 4-b] [1, 3, 4] thiadiazoles; 6-substituted-3-[2-phenylquinol -4-yl]-7H-1, 2, 4-triazolo [3, 4-b] [1, 3, 4] thiadiazines and 7-ethoxycarbonyl and 7-substituted carbamoyl-6-methyl-3-[2-phenylquinol-4-yl] -5H-1, 2, 4-triazolo [3, 4-b] [1, 3, 4] thiadiazines were synthesized and evaluated for antibacterial and antifungal activities