Antimalarial activity of basic phospholipases A2 isolated from Paraguayan Bothrops diporus venom against Plasmodium falciparum

Abstract

Malaria is a parasitic infectious disease and was responsible for 400.000 deaths in 2018. Plasmodium falciparum represents the species that causes most human deaths due to severe malaria. In addition, studies prove the resistance of P. falciparum to drugs used to treat malaria, making the search for new drugs with antiplasmodial potential necessary. In this context, the literature describes snake venoms as a rich source of molecules with microbicidal potential, including phospholipases A 2 (PLA 2 s). In this sense, the present study aimed to isolate basic PLA 2 s from Paraguayan Bothrops diporus venom and evaluate their antiplasmodial potential. Basic PLA 2 s were obtained using two chromatographic steps. Initially, B. diporus venom was subjected to ion exchange chromatography (IEC). The electrophoretic profile of the fractions from the IEC permitted the selection of 3 basic fractions, which were subjected to reverse phase chromatography, resulting in the isolation of the PLA 2 s. The toxins were tested for enzymatic activity using a chromogenic substrate and finally, the antiplasmodial, cytotoxic potential and hemolytic activity of the isolated toxins were evaluated. The electrophoretic profile of the fractions from the IEC permitted the selection of 3 basic fractions, which were subjected to reverse phase chromatography, resulting in the isolation of the two enzymatically active PLA 2 s, BdTX-I and BdTX-II and the PLA 2 homologue BdTX-III. The antiplasmodial potential was evaluated and the toxins showed IC 50 values of: 2.44, 0.0153 and 0.59 μg/mL respectively, presenting PLA 2 selectivity according to the selectivity index results (SI) calculated against HepG2 cells. The results show that the 3 basic phospholipases isolated in this study have a potent antiparasitic effect against the W2 strain of P. falciparum . In view of the results obtained in this work, further research are necessary to determine the mechanism of action by which these toxins cause cell death in parasites.

Purification, Characterization and Evaluation of the Antitumoral Activity of a Phospholipase A2 from the Snake Bothrops moojeni

“…Indirect hemolytic activity was found in sheep blood, when incubated with 47.26 µM of a PLA 2 from the venom of B. alternatus. This information confirms that the pharmacological activities present in PLA 2 do not depend only on the catalytic activity [16,[34][35][36][37][38].…”

From birth to adulthood: An analysis of the Brazilian lancehead (Bothrops moojeni) venom at different life stages

“…Snake venom PLA 2 s from the Viperidae family can be divided into two groups: catalytically active (D-49) and enzymatically inactive (K-49, S-49, R-49, Q-49 and N-49) [ 79 , 92 , 93 ]. The presence of both types of PLA 2 s in different proportions and the variability of catalytic efficiency (specific activity) could explain why the PLA 2 activity in the enzymatic assays did not reflect the increase of PLA 2 found in LC-MS/MS [ 94 , 95 ].…”

Antimalarial efficacy and toxicological assessment of medicinal plant ingredients of Prabchompoothaweep remedy as a candidate for antimalarial drug development

“…The SI value is a crucial parameter for determining whether further work on an extract is warranted [ 35 ]. When the SI results are greater than 10, the extract is considered potentially safe in terms of cytotoxicity parameters [ 36 ]. Therefore, the aqueous T. arjuna extract with an SI value greater than 54.22 suppressed P. falciparum infection without acute toxic effects in mammalian cells.…”