Análise genômica e pós-genômica de proteínas de Leishmania chagasi

As leishmanias são parasitas intracelulares que causam um amplo espectro de doenças, desde lesões cutâneas isoladas até formas viscerais fatais. Apesar dos progressos na epidemiologia, imunologia e bioquímica destas parasitoses. As primeiras 10.000 seqüências de cDNA de Leishmania chagasi, produzidas pelo Programa Genoma Nordeste (ProGeNE), foram analisadas quanto à categorização funcional e conteúdo GC de seqüências codificantes e nãocodificantes, além de ter sido identificado um grupo de genes restritos aos tripanosomatídeos. Foram também analisados dois genes conservados, hsp70 (proteína de choque térmico de 70kDa) e hsp83, que apresentavam seqüência completa. Polipeptídeos recombinantes contendo seqüências de HSP70 progressivamente maiores foram usados em ensaios de imunoadsorção para identificar regiões antigênicas em toda a extensão da proteína. As seqüências de aminoácidos deduzidas para HSP70 e HSP83 foram comparadas com um grande grupo de seqüências similares entre os tripanosomatídeos e entre outros grupos taxonômicos. Os epitopos ou regiões antigênicas, definidos neste estudo mapearam claramente sobre as regiões divergentes. Os sítios precisos de transencadeamento e poli-adenilação para HSP83 foram identificados através de estudos comparativos das regiões 5´- e 3´-não traduzida e das seqüências genômicas correspondentes de HSP83 e de outros genes disponíveis para L. chagasi. Este trabalho espera contribui, portanto, para um melhor entendimento da antigenicidade das HSP nas infecções e para uma definição dos sítios de processamento do RNAm em Leishmani

Antileishmanial activity of warifteine: A bisbenzylisoquinoline alkaloid isolated from cissampelos sympodialis eichl. (Menispermaceae). The Scientific World Journal 2012

chagasi is the etiological agent of visceral leishmaniasis, an important endemic zoonosis in the American continent, as well as in many other countries in Asia, Africa, and Mediterranean Europe. The treatment is difficult due to the high toxicity of the available drugs, high costs, and emergence of resistance in the parasites. Therefore, there is an urgent need for new leishmanicidal agents. The bisbenzylisoquinoline alkaloids have been related to antibacterial, antiprotozoal, and antifungal activities. The aim of this study was to evaluate the growth inhibitory activity of warifteine (bisbenzylisoquinoline alkaloid) against L. chagasi promastigotes in axenic cultures and the occurrence of drug-induced ultrastructural changes in the parasite. This bisbenzylisoquinoline alkaloid was isolated from the leaves and roots of Cissampelos sympodialis Eichl. (Menispermaceae), a plant commonly used for the treatment of various diseases in Brazilian folk medicine. Using the purified warifteine, the 50% inhibitory concentration (IC 50 ) was determined at 0.08 mg/mL after 72 h in culture, inducing significant changes in the parasite morphology, like aberrant multisepted forms and blebs in the plasma membrane. In conclusion, warifteine represents an attractive candidate for future pharmacological studies aiming new leishmanicidal drugs

Antileishmanial Activity of Warifteine: A Bisbenzylisoquinoline Alkaloid Isolated from Cissampelos sympodialis Eichl. (Menispermaceae)

Leishmania (L.) chagasi is the etiological agent of visceral leishmaniasis, an important endemic zoonosis in the American continent, as well as in many other countries in Asia, Africa, and Mediterranean Europe. The treatment is difficult due to the high toxicity of the available drugs, high costs, and emergence of resistance in the parasites. Therefore, there is an urgent need for new leishmanicidal agents. The bisbenzylisoquinoline alkaloids have been related to antibacterial, antiprotozoal, and antifungal activities. The aim of this study was to evaluate the growth inhibitory activity of warifteine (bisbenzylisoquinoline alkaloid) against L. chagasi promastigotes in axenic cultures and the occurrence of drug-induced ultrastructural changes in the parasite. This bisbenzylisoquinoline alkaloid was isolated from the leaves and roots of Cissampelos sympodialis Eichl. (Menispermaceae), a plant commonly used for the treatment of various diseases in Brazilian folk medicine. Using the purified warifteine, the 50% inhibitory concentration (IC50) was determined at 0.08 mg/mL after 72 h in culture, inducing significant changes in the parasite morphology, like aberrant multisepted forms and blebs in the plasma membrane. In conclusion, warifteine represents an attractive candidate for future pharmacological studies aiming new leishmanicidal drugs