Amphibian skin secretions are known as a rich source of biologically active molecules, most of which are alkaloids, biogenic amines, and peptides. Dermaseptins are a class of antimicrobial peptides present in tree frogs of the Phyllomedusa genus. They are cationic molecules of 28-34 residues that permeabilize the membrane of Gram-positive and Gram-negative bacteria, yeasts, and filamentous fungi, showing little or no hemolytic activity. This work reports the isolation, molecular mass analysis, primary structure determination, biological activities, and potential therapeutic applications of an antimicrobial peptide found in the skin secretion of Phyllomedusa oreades, which is a newly described amphibian species endemic of the Brazilian savanna. DS 01 is a 29-residue-long peptide with a molecular mass of 2793.39 Da showing antibacterial properties against Gram-positive and Gram-negative bacteria in the range of 3-25 microm. Anti-protozoan activity was investigated using T. cruzi in its trypomatigote and epimastigote forms cultivated in both cell culture and blood media. Within 2 h after incubation with DS 01 at a final concentration of approximately 6 microm, no protozoan cells were detected. Two synthetic dermaseptins, described previously by our group and named dermadistinctins K and L (DD K and DD L), also had their anti-Trypanosoma cruzi activity investigated and demonstrated similar properties. Toxicity of DS 01 to mouse erythrocytes and white blood cells was evaluated by means of atomic force microscopy and flow cytometry. No morphological alterations were observed at a lytic concentration of DS 01, suggesting its therapeutic value especially as an anti-T. cruzi agent to prevent infections during blood transfusion.
1 January 2005 in Bioorganic & Medicinal Chemistry Letters
Seven lignans isolated from the hexane extract of the leaves of Zanthoxyllum naranjillo (Rutaceae) were tested in both in vitro and in vivo assays against two strains of Trypanosoma cruzi (Bolivia and Y). Of the seven assayed lignans, three were inactive [(+)-sesamin, (+)-piperitol-4′-O-γ,γ-dimethylallyl ether and (-)-3,4-dimethoxy-3′,4′-demethylenedioxycubebin] and three were partially active in the in vitro assays [(-)-hibalactone, (-)-kaerophylin and (-)-cubebin]. Healthy animals developed the disease after injection of the tested infected blood samples containing these three compounds. One compound [(-)-methylpluviatolide] was highly effective in the in vitro assay and healthy animals injected with the tested samples did not develop the disease. Moreover, only (-)-methylpluviatolide was highly active against the bloodstream forms of both strains of T. cruzi for the in vivo assay. However, it was not active against the tissue forms of the parasite.
1 July 2007 in International Journal of Biological Macromolecules