Dye detoxification by Lentinula edodes INCQS 40220

Lentinula edodes belongs to the group of fungi known as ligninolytic fungi, due to its ability to degrade the aromatic structure of the lignin. Textile dyes also have aromatic structure, and after microbial degradation, some of them can be transformed into toxic compounds, when compared to the original structure, representing risk to environment and human health. Therefore, the potential of the fungus L. edodes INCQS 40220 to decolorize and to detoxify reactive red 198 (azo dye), reactive blue 214 (azo dye) and reactive blue 21 (cooper phthalocyanine dye) in a mixture (MXD), was evaluated. After 14 days of incubation, total decolorization in liquid media was obtained. The fungal treatment of MXD did not present toxic effects towards blood human cells. The genotoxicity of MXD, assessed by Comet assay, was efficiently reduced to 61% and in the Ames test presented negative response for mutagenicity for Salmonella enterica serovar Typhimurium TA97, TA98, TA100 and TA102 strains. The results indicated L. edodes INCQS 40220 efficiency on decolorization and genotoxicity reduction of a mixture of different dyes. Therefore, based on these results, obtained under laboratory conditions, L. edodes INCQS 40220 has potential for textile effluent treatment.Título PT: Detoxificação de corante por Lentinula edodes INCQS 40220Lentinula edodes pertence ao grupo de fungos conhecidos como fungos ligninolíticos, devido a sua habilidade de degradar estruturas aromáticas da lignina. Corantes têxteis também possuem estruturas aromáticas e, após a degradação microbiana, alguns destes corantes podem ser transformados em compostos tóxicos quando comparados à estrutura original, representando risco à saúde ambiental e humana. Portanto, o potencial do fungo L. edodes INCQS 40220 para descolorir e detoxificar a mistura de vermelho reativo 198 (corante azo), azul reativo 214 (corante azo) e azul reativo 21 (corante ftalocianina de cobre) foi avaliada (MXD). Após 14 dias de incubação, foi obtida descoloração total em meio líquido. O tratamento fúngico de MXD não apresentou efeitos tóxicos em células sanguíneas humanas. A genotoxicidade de MXD, avaliada por meio do Ensaio Cometa, foi eficientemente reduzida para 61% e, no teste de Ames, apresentou resposta negativa à mutagenicidade para Salmonella enterica serovar Typhimurium TA97, TA98, TA100 e TA102 strains. Os resultados indicaram eficiência de L. edodes INCQS 40220 na descoloração e redução de genotoxicidade na mistura de diferentes corantes. Portanto, com base nos resultados obtidos em condições de laboratório, L. edodes INCQS 40220 tem potencial para o tratamento de efluente têxtil

Megazol and its bioisostere 4H-1,2,4-triazole: comparing the trypanocidal, cytotoxic and genotoxic activities and their in vitro and in silico interactions with the Trypanosoma brucei nitroreductase enzyme

Megazol (7) is a 5-nitroimidazole that is highly active against Trypanosoma cruzi and Trypanosoma brucei, as well as drug-resistant forms of trypanosomiasis. Compound 7 is not used clinically due to its mutagenic and genotoxic properties, but has been largely used as a lead compound. Here, we compared the activity of 7 with its 4H-1,2,4-triazole bioisostere (8) in bloodstream forms of T. brucei and T. cruzi and evaluated their activation by T. brucei type I nitroreductase (TbNTR) enzyme. We also analysed the cytotoxic and genotoxic effects of these compounds in whole human blood using Comet and fluorescein diacetate/ethidium bromide assays. Although the only difference between 7 and 8 is the substitution of sulphur (in the thiadiazole in 7) for nitrogen (in the triazole in 8), the results indicated that 8 had poorer antiparasitic activity than 7 and was not genotoxic, whereas 7 presented this effect. The determination of Vmax indicated that although 8 was metabolised more rapidly than 7, it bounds to the TbNTR with better affinity, resulting in equivalent kcat/KM values. Docking assays of 7 and 8 performed within the active site of a homology model of the TbNTR indicating that 8 had greater affinity than 7

Antinociceptive activity of Stephanolepis hispidus skin aqueous extract depends partly on opioid system activation

Submitted by Alexandre Sousa ([email protected]) on 2014-10-23T13:09:21Z No. of bitstreams: 1 Mar_Drugs_11_1221-1234.pdf: 182058 bytes, checksum: 2901e090d0e728bd217d6d7d3c839433 (MD5)Approved for entry into archive by Alexandre Sousa ([email protected]) on 2014-10-23T13:13:58Z (GMT) No. of bitstreams: 1 Mar_Drugs_11_1221-1234.pdf: 182058 bytes, checksum: 2901e090d0e728bd217d6d7d3c839433 (MD5)Made available in DSpace on 2014-10-23T15:28:15Z (GMT). No. of bitstreams: 1 Mar_Drugs_11_1221-1234.pdf: 182058 bytes, checksum: 2901e090d0e728bd217d6d7d3c839433 (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Instituto de Estudos do Mar Almirante Paulo Moreira. Departamento de Oceanografia. Divisão de Ecosistemas Marinhos. Arraial do Cabo, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil.Stephanolepis hispidus is one of the most common filefish species in Brazil. Its skin is traditionally used as a complementary treatment for inflammatory disorders. However, there are very few studies on chemical and pharmacological properties using the skin of this fish. This study was undertaken in order to investigate the effect of aqueous crude extract of S. hispidus skin (SAE) in different nociception models. Here, we report that intraperitoneal administration of SAE inhibited the abdominal constrictions induced by acetic acid in mice. In addition to the effect seen in the abdominal constriction model, SAE was also able to inhibit the hyperalgesia induced by carrageenan and prostaglandin E2 (PGE2) in mice. This potent antinociceptive effect was observed in the hot plate model too, but not in tail-flick test. Naloxone, an opioid receptor antagonist, was able to block the antinociceptive effect of SAE in the abdominal constriction and hot plate models. In addition, SAE did not present cytotoxic or genotoxic effect in human peripheral blood cells. Our results suggest that aqueous crude extract from S. hispidus skin has antinociceptive activity in close relationship with the partial activation of opioid receptors in the nervous system. Moreover, aqueous crude extract from S. hispidus skin does not present toxicity and is therefore endowed with the potential for pharmacological control of pain

Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group

Nitroimidazoles exhibit high microbicidal activity, but mutagenic, genotoxic and cytotoxic properties have been attributed to the presence of the nitro group. However, we synthesised nitroimidazoles with activity against the trypomastigotes of Trypanosoma cruzi, but that were not genotoxic. Herein, nitroimidazoles (11-19) bearing different substituent groups were investigated for their potential induction of genotoxicity (comet assay) and mutagenicity (Salmonella/Microsome assay) and the correlations of these effects with their trypanocidal effect and with megazol were investigated. The compounds were designed to analyse the role played by the position of the nitro group in the imidazole nucleus (C-4 or C-5) and the presence of oxidisable groups at N-1 as an anion receptor group and the role of a methyl group at C-2. Nitroimidazoles bearing NO2 at C-4 and CH3 at C-2 were not genotoxic compared to those bearing NO 2 at C-5. However, when there was a CH3 at C-2, the position of the NO2 group had no influence on the genotoxic activity. Fluorinated compounds exhibited higher genotoxicity regardless of the presence of CH3 at C-2 or NO2 at C-4 or C-5. However, in compounds 11 (2-CH3; 4-NO2; N-CH2OHCH2Cl) and 12 (2-CH3; 4-NO2; N-CH2OHCH2F), the fluorine atom had no influence on genotoxicity. This study contributes to the future search for new and safer prototypes and provide

In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents

Submitted by Sandra Infurna ([email protected]) on 2019-09-04T13:58:56Z No. of bitstreams: 1 KellySalomao_SolangeCastro_etal_IOC_2019.pdf: 731304 bytes, checksum: adf3685bf6509cf92b26ed34e0f568e0 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-09-04T14:15:45Z (GMT) No. of bitstreams: 1 KellySalomao_SolangeCastro_etal_IOC_2019.pdf: 731304 bytes, checksum: adf3685bf6509cf92b26ed34e0f568e0 (MD5)Made available in DSpace on 2019-09-04T14:15:45Z (GMT). No. of bitstreams: 1 KellySalomao_SolangeCastro_etal_IOC_2019.pdf: 731304 bytes, checksum: adf3685bf6509cf92b26ed34e0f568e0 (MD5) Previous issue date: 2019Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Programa de Pós-Graduação em Vigilância Sanitária. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Programa de Pós-Graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Programa de Pós-Graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese de Fármacos. Farmanguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese de Fármacos. Farmanguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese de Fármacos. Farmanguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Programa de Pós-Graduação em Vigilância Sanitária. Rio de Janeiro, RJ, Brasil.Only benznidazole (Bnz) (1) and nifurtimox (Nfx) (2) are licensed for the treatment of Chagas disease although their safety and efficacy profile are far from ideal. Farmanguinhos from Fiocruz has developed seven nitroimidazole compounds (4-10) analogs of megazol (3). OBJECTIVES To evaluate whether the genotoxic effect of 3 was abolished in the seven nitroimidazoles (4-10) analogs using the in vitro alkaline comet assay (CA) and the in vitro cytokinesis-block micronucleus assay (CBMN) in whole human blood cells (WHBC) and correlate this effect with their trypanocidal activity using bloodstream trypomastigote forms of Trypanosoma cruzi. METHODS The toxicity of 3-10 to WHBC in the in vitro CA was determined using the fluorescein diacetate/ethidium bromide assay. DNA damage in the in vitro CA was evaluated according to tail size in four classes (0-3) and methyl methane-sulfonate (MMS) was used as a positive control. The cytotoxicity of 3-10 to WHBC in the CBMN was measured using the cytokinesis-block proliferation index and the replication index. The number of the micronucleate cells in 2,000 binucleate cells by experimental group was determined. Mitomycin C and N-deacetyl-N-methylcolchicine were used as positive controls. FINDINGS Compound 3 showed a significant DNA strand break effect through the in vitro CA and highly significant clastogenic and/or aneugenic effect in the CBMN. Compounds 5, 6, 8, 9 and 10 showed negative results in the CBMN and positive results in the in vitro CA, while the inverse effect was observed for 4 and 7. MAIN CONCLUSIONS Compound 10 was the most promising to proceed with the development as a drug candidate in the treatment of Chagas disease showing absence of chromosomal cytogenetic damage and high activity against T. cruzi, about two times higher than 3 and the clinical drug 1

Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group

Submitted by Alexandre Sousa ([email protected]) on 2015-07-02T18:25:31Z No. of bitstreams: 1 Mem_Inst_Oswaldo_Cruz_110_492-499.pdf: 731403 bytes, checksum: e3c80a885f8ca653823b2bbdf158f8c5 (MD5)Approved for entry into archive by Alexandre Sousa ([email protected]) on 2015-07-02T18:31:44Z (GMT) No. of bitstreams: 1 Mem_Inst_Oswaldo_Cruz_110_492-499.pdf: 731403 bytes, checksum: e3c80a885f8ca653823b2bbdf158f8c5 (MD5)Approved for entry into archive by Alexandre Sousa ([email protected]) on 2015-07-02T18:52:16Z (GMT) No. of bitstreams: 1 Mem_Inst_Oswaldo_Cruz_110_492-499.pdf: 731403 bytes, checksum: e3c80a885f8ca653823b2bbdf158f8c5 (MD5)Made available in DSpace on 2015-07-02T18:52:16Z (GMT). No. of bitstreams: 1 Mem_Inst_Oswaldo_Cruz_110_492-499.pdf: 731403 bytes, checksum: e3c80a885f8ca653823b2bbdf158f8c5 (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese de Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese de Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Departamento de Biofísica e Biometria. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil.Westfälischen Wilhelms-Universität Münster. Organisch-Chemisches Institut. Münster, Germany.Westfälischen Wilhelms-Universität Münster. Organisch-Chemisches Institut. Münster, Germany.Nitroimidazoles exhibit high microbicidal activity, but mutagenic, genotoxic and cytotoxic properties have been attributed to the presence of the nitro group. However, we synthesised nitroimidazoles with activity against the trypomastigotes of Trypanosoma cruzi, but that were not genotoxic. Herein, nitroimidazoles (11-19) bearing different substituent groups were investigated for their potential induction of genotoxicity (comet assay) and mutagenicity (Salmonella/Microsome assay) and the correlations of these effects with their trypanocidal effect and with megazol were investigated. The compounds were designed to analyse the role played by the position of the nitro group in the imidazole nucleus (C-4 or C-5) and the presence of oxidisable groups at N-1 as an anion receptor group and the role of a methyl group at C-2. Nitroimidazoles bearing NO2 at C-4 and CH3 at C-2 were not genotoxic compared to those bearing NO 2 at C-5. However, when there was a CH3 at C-2, the position of the NO2 group had no influence on the genotoxic activity. Fluorinated compounds exhibited higher genotoxicity regardless of the presence of CH3 at C-2 or NO2 at C-4 or C-5. However, in compounds 11 (2-CH3; 4-NO2; N-CH2OHCH2Cl) and 12 (2-CH3; 4-NO2; N-CH2OHCH2F), the fluorine atom had no influence on genotoxicity. This study contributes to the future search for new and safer prototypes and provide