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

Abstract

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.

Key words:
snake serum; Crotalus durissus collilineatus; phospholipase A₂ inhibitors; CdcPLI; leishmaniasis treatment