Inhibition of malaria parasite Plasmodium falciparum development by crotamine, a cell penetrating peptide from the snake venom

We show here that crotamine, a polypeptide from the South American rattlesnake venom with cell penetrating and selective anti-fungal and anti-tumoral properties, presents a potent anti-plasmodial activity in culture. Crotamine inhibits the development of the Plasmodium falciparum parasites in a dose-dependent manner [IC50 value of 1.87 mu M], and confocal microscopy analysis showed a selective internalization of fluorescent-labeled crotamine into P. falciparum infected erythrocytes, with no detectable fluorescence in uninfected healthy erythrocytes. In addition, similarly to the crotamine cytotoxic effects, the mechanism underlying the anti-plasmodial activity may involve the disruption of parasite acidic compartments H+ homeostasis. In fact, crotamine promoted a reduction of parasites organelle fluorescence loaded with the lysosomotropic fluorochrome acridine orange, in the same way as previously observed mammalian tumoral cells. Taken together, we show for the first time crotamine not only compromised the metabolism of the P. falciparum, but this toxin also inhibited the parasite growth. Therefore, we suggest this snake polypeptide as a promising lead molecule for the development of potential new molecules, namely peptidomimetics, with selectivity for infected erythrocytes and ability to inhibit the malaria infection by its natural affinity for acid vesicles. (C) 2016 Elsevier Inc. All rights reserved.Fundacao de Amparo Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Univ Fed Sao Paulo UNIFESP, Dept Biofis, BR-04044020 Sao Paulo, BrazilUniv Fed Sao Paulo UNIFESP, Dept Farmacol, Rua 3 de Maio 100,Ed INFAR,3rd Floor, BR-04044020 Sao Paulo, BrazilUniv Sao Paulo USP RP, Dept Bioquim & Imunol, Ribeirao Preto, BrazilUniv Fed Sao Paulo UNIFESP, Dept Biociencias, Rua Silva Jardim 136, BR-11015020 Santos, SP, BrazilUniv Fed Sao Paulo UNIFESP, Dept Biofis, BR-04044020 Sao Paulo, BrazilUniv Fed Sao Paulo UNIFESP, Dept Farmacol, Rua 3 de Maio 100,Ed INFAR,3rd Floor, BR-04044020 Sao Paulo, BrazilUniv Fed Sao Paulo UNIFESP, Dept Biociencias, Rua Silva Jardim 136, BR-11015020 Santos, SP, BrazilWeb of Scienc