Avaliação do potencial tripanocida de diaminas, diaminas de ferroceno e derivados de 1,4-naftoquinonas em cepas de Trypanosoma brucei
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Data
2013-02-25
Autores
Arenas Velásquez, Angela Maria [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Trypanosoma brucei é o agente etiológico da tripanossomíase africana ou doença do sono, transmitida por dípteros do gênero Glossina, conhecidos como moscas tsé-tsé. O diagnóstico e tratamento da doença não são satisfatórios, uma vez que para o tratamento está disponível um número de drogas altamente tóxicas e com um efeito limitado, pois dependem da fase da doença, das condições fisiológicas do hospedeiro, da suscetibilidade e variabilidade genética da cepa. Além do alto custo, o tratamento é potencialmente perigoso e está limitado ao surgimento de resistência generalizada aos fármacos utilizados. O diagnóstico é limitado à associação dos sintomas com a doença, muitas vezes é confundido com outras doenças pelo que o paciente não recebe o tratamento adequado. Por isso, tem-se a necessidade de buscar novos fármacos com melhor atividade tripanocida. Neste trabalho, avaliou-se a atividade tripanocida de 38 compostos diferentes e inéditos, como N1,N2-dibenziletano-1,2-diamina (cloridratos de benzil diaminas), N1-benzil,N2-metilferroceniletano-1,2-diamina (cloridratos de diaminas de ferroceno), 2-metoxi/hidroxi-3-(1-alquenil)-1,4-naftoquinonas e seus derivados 2-amina-1,4-naftoquinonas contra as cepas 427 e 29-13 de T. brucei. A eficácia dos compostos foi avaliada pelo método colorimétrico do MTT [brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazoliom]. Os resultados encontrados foram similares aos das atividades metabólicas das células (parasitas e/ou células HepG2 - linhagem de células de hepatoma, usada como modelo para simular funções hepáticas humanas in vitro), sendo o IC50 (metade da concentração inibitória máxima) calculado por regressão linear para cada composto. Da série anterior, o composto cloridrato de...
Trypanosoma brucei is the etiologic agent of sleeping sickness (Human African Trypanosomiasis [HAT]), transmitted by flies of Glossina genus, known as tsetse flies. The diagnostic and treatment of this disease are not satisfactory, since the treatment uses many toxicity drugs with limited effects, because depend on the stage of the disease, morphological diversity, heterogeneous biological behaviour, different clinical courses and the virulence appears to be an intrinsic property of each strain and high genetic variability. Besides the high cost, the treatment is potentially dangerous and limited the emergence of widespread drug resistance. The diagnosis is limited to the association of symptoms with the disease, is often confused with other diseases so the patient does not receive adequate treatment. Thus, the development of new research is necessary in order to generate new drugs with trypanocidal activity. In this work, we evaluated the trypanocidal activity of 38 inedited compounds of N1,N2-dibenzylethane-1,2-diamine hydrochlorides, N1-benzyl,N2-methyferrocenylethane-1,2-diamine hydrochlorides, 2-metoxy/hydroxy-3-(1-alquenyl)-1,4-naphtoquinones and amine derivatives of this compounds (2-amine-1,4-naphtoquinones) against 427 and 29-13 T. brucei parasite strains. The efficacy of these compounds was also measured using the reduction of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]. The results were similar to the metabolic activity of cells (parasites and/or HepG2 - hepatoma cell line used as a model to simulate human hepatic functions in vitro), being the IC50 (half of the maximum inhibitory concentration) calculated by linear regression for each sample. The compounds N-(ferrocenylmetyl)-N’-(4-metoxybenzyl)ethane-1,2-diamine) hydrochlorides and 2-metoxy-3-(2-phenylethenyl)-1,4-naphtoquinone... (Complete abstract click electronic access below)
Trypanosoma brucei is the etiologic agent of sleeping sickness (Human African Trypanosomiasis [HAT]), transmitted by flies of Glossina genus, known as tsetse flies. The diagnostic and treatment of this disease are not satisfactory, since the treatment uses many toxicity drugs with limited effects, because depend on the stage of the disease, morphological diversity, heterogeneous biological behaviour, different clinical courses and the virulence appears to be an intrinsic property of each strain and high genetic variability. Besides the high cost, the treatment is potentially dangerous and limited the emergence of widespread drug resistance. The diagnosis is limited to the association of symptoms with the disease, is often confused with other diseases so the patient does not receive adequate treatment. Thus, the development of new research is necessary in order to generate new drugs with trypanocidal activity. In this work, we evaluated the trypanocidal activity of 38 inedited compounds of N1,N2-dibenzylethane-1,2-diamine hydrochlorides, N1-benzyl,N2-methyferrocenylethane-1,2-diamine hydrochlorides, 2-metoxy/hydroxy-3-(1-alquenyl)-1,4-naphtoquinones and amine derivatives of this compounds (2-amine-1,4-naphtoquinones) against 427 and 29-13 T. brucei parasite strains. The efficacy of these compounds was also measured using the reduction of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]. The results were similar to the metabolic activity of cells (parasites and/or HepG2 - hepatoma cell line used as a model to simulate human hepatic functions in vitro), being the IC50 (half of the maximum inhibitory concentration) calculated by linear regression for each sample. The compounds N-(ferrocenylmetyl)-N’-(4-metoxybenzyl)ethane-1,2-diamine) hydrochlorides and 2-metoxy-3-(2-phenylethenyl)-1,4-naphtoquinone... (Complete abstract click electronic access below)
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Palavras-chave
Biotecnologia, Disturbios do sono, Parasitologia, Sleep disturbances
Como citar
ARENAS VELÁSQUEZ, Angela Maria. Avaliação do potencial tripanocida de diaminas, diaminas de ferroceno e derivados de 1,4-naftoquinonas em cepas de Trypanosoma brucei. 2013. 74 f. Dissertação (mestrado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Instituto de Química de Araraquara, 2013.