Mesoionic compounds with antifungal activity against Fusarium verticillioides

Made available in DSpace on 2015-08-19T13:49:22Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) rojane_paiva_etal_IOC_2015.pdf: 631223 bytes, checksum: f314e4b6c94c272cb5ffd3cc30ffb3e3 (MD5) Previous issue date: 2015Universidade Federal Rural do Rio de Janeiro. Instituto de Ciências Exatas. Departamento de Química. Seropédica, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Taxonomia Bioquímica e Bioprospecção de Fungos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Taxonomia Bioquímica e Bioprospecção de Fungos. Rio de Janeiro, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro. Instituto de Ciências Exatas. Departamento de Química. Seropédica, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro. Instituto de Ciências Exatas. Departamento de Química. Seropédica, RJ, Brasil.Background: Fungi contaminate the food of humans and animals, are a risk to health, and can cause financial losses. In this work, the antifungal activities of 16 mesoionic compounds (MI 1–16) were evaluated against mycotoxigenic fungi, including Aspergillus spp., Fusarium verticillioides and Penicillium citrinum. Furthermore, the decreased ergosterol in the total lipid content of Fusarium verticillioides was investigated. Results: F. verticillioides was the most sensitive fungus to the mesoionic compounds. Among the evaluated compounds, MI-11 and MI-16 presented higher antifungal effects against F. verticillioides, with MIC values of 7.8 μg/ml, and MI-2 and MI-3 followed, with MICs of 15.6 μg/ml. The most active compounds were those with heterocyclic ring phenyl groups substituted by electron donor moieties (MI-11 and MI-16). Among some compounds with higher activity (MI-2, MI-11 and MI-16), decreased ergosterol content in the total lipid fraction of F. verticillioides was demonstrated. MI-2 reduced the ergosterol content approximately 40% and 80% at concentrations of 7.8 μg/ml and 15.6 μg/ml, respectively, and MI-11 and MI-16 decreased the content by 30% and 50%, respectively, when at a concentration of 7.8 μg/ml. Conclusion: These findings indicate that mesoionic compounds have significant antifungal activity against F. verticillioides

Atividade antibacteriana de novas 2-Amino-1,4-Naftoquinonas / Anti-bacterial activity of new 2-Amino-1,4-Naphthoquinones

Vários compostos que possuem esqueleto de 1,4-naftoquinona são amplamente estudados, principalmente no desenvolvimento de novos fármacos. Sua atividade biológica é atribuída à sua capacidade de atuar no transporte de elétrons e, a partir da geração de espécies reativas de oxigênio (ROS) como peróxido de hidrogênio, radicais hidroxila e ânions radicais superóxidos, induzem estresse oxidativo nas células. Este processo é irreversível, pois causa danos permanentes aos ácidos nucléicos e proteínas essenciais. Além disso, a incorporação do átomo de N em C-2 e C-3 da estrutura de 1,4-naftoquinona levou a compostos com atividades biológicas diversificadas, incluindo a antibacteriana. Neste trabalho uma série de 2-amino-1,4-naftoquinonas foi sintetizada e sua atividade antibacteriana foi avaliada contra nove cepas bacterianas incluindo Gram-positivas e Gram-negativas

Atividade antifúngica de tiosemicarbazonas e semicarbazonas frente a fungos micotoxigênicos

Made available in DSpace on 2015-06-08T14:01:55Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) lucimar_kneippetal_IOC_2014.pdf: 589601 bytes, checksum: 1972577d821dce7fc9ec4ab74e6ed50e (MD5) Previous issue date: 2014Universidade Federal Rural do Rio de Janeiro/UFRRJ. Departamento de Química. Seropédica, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro/UFRRJ. Departamento de Química. Seropédica, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro/UFRRJ. Departamento de Química. Seropédica, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro/UFRRJ. Departamento de Química. Seropédica, RJ, Brasil.Os fungos micotoxigênicos podem comprometer a qualidade dos alimentos colocando em risco a saúde do homem e dos animais. As atividades antifúngicas de oito tiosemicarbazonas (1-8) e nove semicarbazonas (9-17) foram avaliadas frente Aspergillus flavus, A. nomius, A. ochraceus, A. parasiticus e Fusarium verticillioides. As tiosemicarbazonas apresentaram valores de MIC entre 125 a 500 mg/ml. As tiosemicarbazonas 1 e 2 exerceram atividade fungistática frente Aspergillus spp., e enquanto, a substância 2 apresentou atividade fungicida frente F. verticillioides. O composto 2 também foi capaz de apresentar efeito quelante (63%) frente ao ferro e, reduzir 28 e 71% o conteúdo de ergosterol de A. parasiticus nas concentrações de 31,2 e 62,5 mg/ml, respectivamente. Os resultados obtidos para a atividade antifúngica revelaram que a classe das tiossemicarbazonas foi mais ativa quando comparada a classe das semicarbazones e, a tiossemicarbazona 2 foi mais ativa frente Aspergillus spp.Mycotoxigenic fungi can compromise the quality of food, exposing human and animal health at risk. The antifungal activity of eight thiosemicarbazones (1-8) and nine semicarbazones (9-17) was evaluated against Aspergillus flavus, A. nomius, A. ochraceus, A. parasiticus and Fusarium verticillioides. Thiosemicarbazones had MIC values of 125-500 μg/ml. The thiosemicarbazones 1 and 2 exerted fungistatic activity against Aspergillus spp., and thiosemicarbazone 2 exerted fungicidal activity against F. verticillioides. Compound 2 showed an iron chelating effect of 63%. The ergosterol content of A. parasiticus had a decrease of 28 and 71% for the 31.2 and 62.5 μg/ml concentrations of thiosemicarbazone 2 compared to the control. The obtained results of antifungal activity revealed that thiosemicarbazone class was more active when compared to semicarbazone class and, the thiosemicarbazone 2 was the most active compound, specially, against Aspergillus spp

Synthetic (E)-3-Phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium Chloride Derivatives as Promising Chemotherapy Agents on Cell Lines Infected with HTLV-1

Synthesis of four compounds belonging to mesoionic class, (E)-3-phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium chloride derivatives (5a–d) and their biological evaluation against MT2 and C92 cell lines infected with human T-cell lymphotropic virus type-1 (HTLV-1), which causes adult T-cell leukemia/lymphoma (ATLL), and non-infected cell lines (Jurkat) are reported. The compounds were obtained by convergent synthesis under microwave irradiation and the cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Results showed IC50 values of all compounds in the range of 1.51–7.70 μM in HTLV-1-infected and non-infected cells. Furthermore, it was observed that 5b could induce necrosis after 24 h for Jurkat and MT2 cell lines. The experimental (fluorimetric method) and theoretical (molecular docking) results suggested that the mechanism of action for 5b could be related to its capacity to intercalate into DNA. Moreover, the preliminary pharmacokinetic profile of the studied compounds (5a–d) was obtained through human serum albumin (HSA) binding affinity using multiple spectroscopic techniques (circular dichroism, steady-state and time-resolved fluorescence), zeta potential and molecular docking calculations. The interaction HSA:5a–d is spontaneous and moderate (Ka ~ 104 M−1) via a ground-state association, without significantly perturbing both the secondary and surface structures of the albumin in the subdomain IIA (site I), indicating feasible biodistribution in the human bloodstream

Microwave-Assisted Synthesis of New N1,N4-Substituted Thiosemicarbazones

We present an efficient procedure for the synthesis of thirty-six N1,N4-substituted thiosemicarbazones, including twenty-five ones that are reported for the first time, using a microwave-assisted methodology for the reaction of thiosemicarbazide intermediates with aldehydes in the presence of glacial acetic acid in ethanol and under solvent free conditions. Overall reaction times (20–40 min when ethanol as solvent, and 3 min under solvent free conditions) were much shorter than with the traditional procedure (480 min); satisfactory yields and high-purity compounds were obtained. The thiosemicarbazide intermediates were obtained from alkyl or aryl isothiocyanates and hydrazine hydrate or phenyl hydrazine by stirring at room temperature for 60 min or by microwave irradiation for 30 min, with lower yields for the latter. The preliminary in vitro antifungal activity of thiosemicarbazones was evaluated against Aspergillus parasiticus and Candida albicans

Organ-related cigarette smoke-induced oxidative stress is strain-dependent.

Background: Cigarette smoke (CS) is associated with oxidative stress in several organs because it contains high concentrations of free radicals and reactive oxygen species. Experimental models, using different strains, provide important insights into the genetic basis of diseases. This study sought to identify, in different mouse strains, the organ that is most-susceptible to CS-induced oxidative stress to obtain an optimized experimental animal model of oxidative injury induced by CS. Material/Methods: Male Swiss, DBA/2, C3H, BALB/c, and C57BL/6 mice were exposed to CS 3 times a day (4 cigarettes per session) for 60 consecutive days. Control groups from the same strains were sham-treated. Protein content, malondialdehyde level, myeloperoxidase activity, and nitrite level were assayed in lung, liver, kidney, and brain from all strains. Catalase and glutathione peroxidase activities were measured. Analyses of data were done by using a 1-way ANOVA with Bonferroni?s post-test (P<.05). Results: Cigarette smoke exposure resulted in distinct, organ-specific responses among strains. The survival rate of DBA/2 mice was lowest. BALB/c and C57BL/6 strains were more-susceptible to oxidative damage in the lung and liver. C3H and C57BL/6 mice were more-susceptible to oxidative damage in the brain. No renal oxidative damage was seen. Conclusions: Mouse strains and individual organs display a range of susceptibilities to CS-induced oxidative stress. BALB/c and C57BL/6 strains appear to be the best choices as experimental models for studying CS effects on liver and lung, and C3H and C57BL/6 strains for CS-effects on the brain