RESUMO
A series of 28 compounds, 3-nitro-1H-1,2,4-triazole, were synthesized by click-chemistry with diverse substitution patterns using medicinal chemistry approaches, such as bioisosterism, Craig-plot, and the Topliss set with excellent yields. Overall, the analogs demonstrated relevant in vitro antitrypanosomatid activity. Analog 15g (R1 = 4-OCF3-Ph, IC50 = 0.09 µM, SI = >555.5) exhibited an outstanding antichagasic activity (Trypanosoma cruzi, Tulahuen LacZ strain) 68-fold more active than benznidazole (BZN, IC50 = 6.15 µM, SI = >8.13) with relevant selectivity index, and suitable LipE = 5.31. 15g was considered an appropriate substrate for the type I nitro reductases (TcNTR I), contributing to a likely potential mechanism of action for antichagasic activity. Finally, 15g showed nonmutagenic potential against Salmonella typhimurium strains (TA98, TA100, and TA102). Therefore, 3-nitro-1H-1,2,4-triazole 15g is a promising antitrypanosomatid candidate for in vivo studies.
Assuntos
Doença de Chagas , Leishmaniose , Tripanossomicidas , Trypanosoma cruzi , Humanos , Relação Estrutura-Atividade , Doença de Chagas/tratamento farmacológico , Triazóis/químicaRESUMO
New treatment approaches targeting cutaneous leishmaniasis (CL) are required since conventional drugs exhibit limitations due to their several adverse effects and toxicity. In this study, we aimed to evaluate the in vivo intralesional treatment efficacy of five isoxazole derivatives previously synthesized and effective in vitro against intracellular amastigote forms of Leishmania (L.) amazonensis. Among the tested analogues, 7 exhibited relevant in vivo therapeutic effects. The in silico predictions provided interesting information about the toxicity, suggesting the safety of analogue 7. Experiments performed with Salmonella typhimurium strains (TA98, TA100, and TA102) showed a non-mutagenicity profile of 7. The treatment of Leishmania-infected BALB/c mice with isoxazole 7 showed remarkably smaller CL lesions and decreased the parasitism (by 98.4%) compared to the control group. Hence, analogue 7 is a promising drug candidate and alternative treatment for CL caused by L. amazonensis.
Assuntos
Antiprotozoários , Leishmania , Leishmaniose Cutânea , Lignanas , Animais , Camundongos , Isoxazóis/farmacologia , Lignanas/farmacologia , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/patologia , Antiprotozoários/farmacologia , Camundongos Endogâmicos BALB CRESUMO
Cryptococcus gattii is an etiologic agent of cryptococcosis and a serious disease that affects immunocompromised and immunocompetent patients worldwide. The therapeutic arsenal used to treat cryptococcosis is limited to a few antifungal agents, and the ability of C. gattii to form biofilms may hinder treatment and decrease its susceptibility to antifungal agents. The objective of this study was to evaluate the antifungal and antibiofilm activities of an ethanolic extract of Cochlospermum regium (Schrank) Pilger leaves against C. gattii. The antifungal activity was assessed by measuring the minimum inhibitory concentration (MIC) using the broth microdilution technique and interaction of the extract with fluconazole was performed of checkerboard assay. The antibiofilm activity of the extract was evaluated in 96-well polystyrene microplates, and the biofilms were quantified by counting colony forming units. The extract showed antifungal activity at concentrations of 62.5 to 250 µg/mL and when the extract was evaluated in combination with fluconazole, C. gattii was inhibited at sub-MIC levels. The antibiofilm activity of the extract against C. gattii was observed both during biofilm formation and on an already established biofilm. The results showed that the ethanolic extract of the leaves of C. regium shows promise for the development of antifungal drugs to treat cryptococcosis and to combat C. gattii biofilms.
Assuntos
Biofilmes/efeitos dos fármacos , Bixaceae/química , Cryptococcus gattii/efeitos dos fármacos , Etanol/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Antifúngicos/farmacologia , Fluconazol/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Myracrodruon urundeuva is a plant native to Brazil, which is used by the indigenous population for the treatment of candidiasis. The aims of this study were to evaluate the antifungal activity of extract against human vaginal Candida species and evaluate the possible toxicological activities of M. urundeuva. Initially, ethanol extracts, ethyl acetate fractions, and hydroalcoholic fractions of the bark and leaf of M. urundeuva were used to determine the minimum inhibitory concentration. The extracts that showed antifungal activity were characterized by liquid chromatography and subjected to toxicity assessment. Toxic, cytotoxic, genotoxic, and mutagenic testing were performed using Allium cepa and Ames assays with the ethanol extracts of the bark and leaves. Hemolytic activity was evaluated in erythrocytes and acute toxicity in rats. The ethanol bark extracts showed best activity against Candida albicans, C. krusei, and C. tropicalis ATCC (4-512 µg/mL). Chemical characterization indicated the presence of flavonoids and tannins in the extracts. Hemolytic activity, genotoxicity, and mutagenicity were not observed. The results of the Ames and A. cepa tests were also in agreement, ethanol bark extracts and ethanol leaf extracts of M. urundeuva showed absence of mutagenic activity. Similar results were observed in the A. cepa assay and acute toxicity test in rats. M. urundeuva bark extracts showed potential for the treatment of vaginal infections caused Candida species, as a topical.
Assuntos
Anacardiaceae/química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Antifúngicos/isolamento & purificação , Brasil , Feminino , Flavonoides/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Casca de Planta/química , Ratos , Taninos/farmacologiaRESUMO
ABSTRACT Myracrodruon urundeuva is a plant native to Brazil, which is used by the indigenous population for the treatment of candidiasis. The aims of this study were to evaluate the antifungal activity of extract against human vaginal Candida species and evaluate the possible toxicological activities of M. urundeuva. Initially, ethanol extracts, ethyl acetate fractions, and hydroalcoholic fractions of the bark and leaf of M. urundeuva were used to determine the minimum inhibitory concentration. The extracts that showed antifungal activity were characterized by liquid chromatography and subjected to toxicity assessment. Toxic, cytotoxic, genotoxic, and mutagenic testing were performed using Allium cepa and Ames assays with the ethanol extracts of the bark and leaves. Hemolytic activity was evaluated in erythrocytes and acute toxicity in rats. The ethanol bark extracts showed best activity against Candida albicans, C. krusei, and C. tropicalis ATCC (4-512 µg/mL). Chemical characterization indicated the presence of flavonoids and tannins in the extracts. Hemolytic activity, genotoxicity, and mutagenicity were not observed. The results of the Ames and A. cepa tests were also in agreement, ethanol bark extracts and ethanol leaf extracts of M. urundeuva showed absence of mutagenic activity. Similar results were observed in the A. cepa assay and acute toxicity test in rats. M. urundeuva bark extracts showed potential for the treatment of vaginal infections caused Candida species, as a topical.
Assuntos
Humanos , Animais , Feminino , Ratos , Candida albicans/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Anacardiaceae/química , Antifúngicos/farmacologia , Taninos/farmacologia , Flavonoides/farmacologia , Brasil , Testes de Sensibilidade Microbiana , Casca de Planta/química , Antifúngicos/isolamento & purificaçãoRESUMO
The present work sought to detect the presence of Pseudomonas spp. at different stages of an effluent treatment plant using the Australian system of stabilization ponds, and to determine the susceptibility of those isolates to different antimicrobials. Thirty-four isolates of Pseudomonas spp. derived from effluent treatment station water samples were collected near the transfer ducts between the ponds in November/2008 and december/2009. Among the Pseudomonas spp. isolates, 47.05 % showed susceptibility to all antimicrobials tested, 20.58 % were resistant to cefepime, and 24 % showed intermediate resistance to streptomycin. No Pseudomonas spp. isolates were found in the final pond, or in post-treatment effluents. The Pseudomonas spp. isolates did not exhibit multiresistance to the antimicrobials tested.
Assuntos
Matadouros , Resistência Microbiana a Medicamentos , Pseudomonas/efeitos dos fármacos , Sus scrofa/microbiologia , Animais , Antibacterianos/farmacologia , Brasil , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Resíduos Industriais , Eliminação de Resíduos de Serviços de Saúde/métodos , Pseudomonas/classificação , Pseudomonas/isolamento & purificação , Estudos Retrospectivos , Especificidade da Espécie , Suínos , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/microbiologia , Microbiologia da ÁguaRESUMO
The present work sought to detect the presence of Pseudomonas spp. at different stages of an effluent treatment plant using the Australian system of stabilization ponds, and to determine the susceptibility of those isolates to different antimicrobials. Thirty-four isolates of Pseudomonas spp. derived from effluent treatment station water samples were collected near the transfer ducts between the ponds in November/2008 and december/2009. Among the Pseudomonas spp. isolates, 47.05
showed susceptibility to all antimicrobials tested, 20.58
were resistant to cefepime, and 24
showed intermediate resistance to streptomycin. No Pseudomonas spp. isolates were found in the final pond, or in post-treatment effluents. The Pseudomonas spp. isolates did not exhibit multiresistance to the antimicrobials tested.
Assuntos
Matadouros , Pseudomonas/efeitos dos fármacos , Resistência Microbiana a Medicamentos , Sus scrofa/microbiologia , Animais , Antibacterianos/farmacologia , Brasil , Eliminação de Resíduos Líquidos/métodos , Eliminação de Resíduos de Serviços de Saúde/métodos , Especificidade da Espécie , Estudos Retrospectivos , Microbiologia da Água , Pseudomonas/classificação , Pseudomonas/isolamento & purificação , Resíduos Industriais , Suínos , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Águas Residuárias/microbiologiaRESUMO
The present work sought to detect the presence of Pseudomonas spp. at different stages of an effluent treatment plant using the Australian system of stabilization ponds, and to determine the susceptibility of those isolates to different antimicrobials. Thirty-four isolates of Pseudomonas spp. derived from effluent treatment station water samples were collected near the transfer ducts between the ponds in November/2008 and december/2009. Among the Pseudomonas spp. isolates, 47.05
showed susceptibility to all antimicrobials tested, 20.58
were resistant to cefepime, and 24
showed intermediate resistance to streptomycin. No Pseudomonas spp. isolates were found in the final pond, or in post-treatment effluents. The Pseudomonas spp. isolates did not exhibit multiresistance to the antimicrobials tested.