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Effect of different serine protease inhibitors in validating the 115 kDa Leishmania donovani secretory serine protease as chemotherapeutic target.
Indian J Biochem Biophys ; 2015 Feb; 52 (1): 14-22
Artículo en Inglés | IMSEAR | ID: sea-157950
ABSTRACT
Proteases have been considered as an important group of targets for development of antiprotozoal drugs due to their essential roles in host-parasite interactions, parasite immune evasion, life cycle transition and pathogenesis of parasitic diseases. The development of potent and selective serine protease inhibitors targeting L. donovani secretory serine protease (pSP) could pave the way to the discovery of potential antileishmanial drugs. Here, we employed different classical serine protease inhibitors (SPIs), such as aprotinin, N-tosyl-l-phenylalanine chloromethyl ketone (TPCK), N-tosyl-lysine chloromethyl ketone (TLCK), benzamidine (Bza) and pSP-antibody to determine the role of the protease in parasitic survival, growth and infectivity. Among the different classical SPIs, aprotinin appeared to be more potent in arresting L. donovani promastigotes growth with significant morphological alterations. Furthermore, aprotinin and anti-pSP treated parasites significantly decreased the intracellular parasites and percentage of infected macrophages. These results suggest that SPIs may reduce the infectivity by targeting the serine protease activity and may prove useful to elucidate defined molecular mechanisms of pSP, as well as for the development of novel antileishmanial drugs in future.
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Texto completo: Disponible Índice: IMSEAR (Asia Sudoriental) Asunto principal: Leishmania donovani / Leishmaniasis / Proteínas Protozoarias / Inhibidores de Serina Proteinasa / Vacunas contra la Leishmaniasis / Serina Proteasas / Antiprotozoarios Idioma: Inglés Revista: Indian J Biochem Biophys Año: 2015 Tipo del documento: Artículo

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Texto completo: Disponible Índice: IMSEAR (Asia Sudoriental) Asunto principal: Leishmania donovani / Leishmaniasis / Proteínas Protozoarias / Inhibidores de Serina Proteinasa / Vacunas contra la Leishmaniasis / Serina Proteasas / Antiprotozoarios Idioma: Inglés Revista: Indian J Biochem Biophys Año: 2015 Tipo del documento: Artículo