Antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, on Leishmania (Leishmania) amazonensis



Título del documento: Antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, on Leishmania (Leishmania) amazonensis
Revue: Memorias do Instituto Oswaldo Cruz
Base de datos: PERIÓDICA
Número de sistema: 000459436
ISSN: 0074-0276
Autores: 1
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Instituciones: 1Universidade Federal de Uberlandia, Instituto de Biotecnologia, Uberlandia, Minas Gerais. Brasil
2Universidade Federal da Bahia, Instituto de Biociencias, Vitoria da Conquista, Bahia. Brasil
3Universidade Federal de Uberlandia, Instituto de Ciencias Biomedicas, Uberlandia, Minas Gerais. Brasil
4Universidade Federal de Sao Paulo, Escola Paulista de Medicina, Sao Paulo. Brasil
5Instituto Butantan, Laboratorio de Imunopatologia, Sao Paulo. Brasil
6Universidade de Sao Paulo, Instituto de Quimica, Sao Paulo. Brasil
7Instituto Butantan, Laboratório de Herpetologia, Sao Paulo. Brasil
Año:
Volumen: 118
País: Brasil
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Experimental, aplicado
Resumen en inglés BACKGROUND Leishmaniasis, a neglected disease caused by the parasite Leishmania, is treated with drugs associated with high toxicity and limited efficacy, in addition to constant reports of the emergence of resistant parasites. In this context, snake serums emerge as good candidates since they are natural sources with the potential to yield novel drugs. OBJECTIVES We aimed to show the antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, against Leishmania (Leishmania) amazonensis. METHODS Promastigotes forms were exposed to γCdcPLI, and we assessed the parasite viability and cell cycle, as well as invasion and proliferation assays. FINDINGS Despite the low cytotoxicity effect on macrophages, our data indicate that γCdcPLI has a direct effect on parasites promoting an arrest in the G1 phase and reduction in the G2/M phase at the highest dose tested. Moreover, this PLA2 inhibitor reduced the parasite infectivity when promastigotes were pre-treated. Also, we demonstrated that the γCdcPLI treatment modulated the host cell environment impairing early and late steps of the parasitism. MAIN CONCLUSIONS γCdcPLI is an interesting tool for the discovery of new essential targets on the parasite, as well as an alternative compound to improve the effectiveness of the leishmaniasis treatment
Disciplinas: Medicina,
Química
Palabras clave: Química farmacéutica,
Suero,
Veneno de víbora,
Inhibidores enzimáticos,
Fosfolipasa A2,
Actividad biológica,
Leishmaniasis,
Crotalus durissus collilineatus
Keyword: Medicinal chemistry,
Snake venom,
Serum,
Enzyme inhibitors,
Phospholipase A2,
Biological activity,
Crotalus durissus collilineatus,
Leishmaniasis
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