Dehydrobufotenin extracted from the Amazonian toad (Anura: Bufonidae) as a prototype molecule for the development of antiplasmodial drugs.

Background: The resistance against antimalarial drugs represents a global challenge in the fight and control of malaria. The Brazilian biodiversity can be an important tool for research and development of new medicinal products. In this context, toxinology is a multidisciplinary approach on the development of new drugs, including the isolation, purification, and evaluation of the pharmacological activities of natural toxins. The present study aimed to evaluate the cytotoxicity, as well as the antimalarial activity and of four compounds isolated from venom as potential oral drug prototypes.

Methods: Four compounds were challenged against 35 target proteins from and screened to evaluate their physicochemical properties using docking assay in Brazilian Malaria Molecular Targets (BraMMT) software and assay in OCTOPUS® software. The antimalarial activity of the compounds against the 3D7 clones were assessed using the SYBR Green I based assay (IC). For the cytotoxic tests, the LD was determined in human pulmonary fibroblast cell line using the [3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay.

Results: All compounds presented a ligand-receptor interaction with ten -related protein targets, as well as antimalarial activity against chloroquine resistant strain (IC = 3.44 μM to 19.11 μM). Three of them (dehydrobufotenine, marinobufagin, and bufalin) showed adequate conditions for oral drug prototypes, with satisfactory prediction of absorption, permeability, and absence of toxicity. In the cell viability assay, only dehydrobufotenin was selective for the parasite.

Conclusions: Dehydrobufotenin revealed to be a potential oral drug prototype presenting adequate antimalarial activity and absence of cytotoxicity, therefore should be subjected to further studies.