Chagas' disease is a parasitic disease with unsatisfactory treatment, mainly in chronic stage. This study aimed to evaluate the trypanocidal activity and action mechanisms of α/β-amyrin and its semisynthetic derivatives, together with four isolated natural triterpenes, tested against trypomastigote and amastigote forms. The structure-activity relationship was suggested and cytotoxicity was measured. In general, greater polar compounds may have improved the selectivity to the protozoan. Action mechanisms were only performed for the amastigotes of Trypanosoma cruzi by evaluating the ultrastructural alterations, membrane permeability, mitochondrial membrane potential and cell volume, since the majority of compounds displayed promising antiamastigote activities. Triterpenes promoted changes on mitochondrial membrane potential and ultrastructural features that suggest autophagy processes. Both combinations between α/β-amyrin and 3-O-acetyl-11-oxo-α/β-amyrin and 3-O-acetyl-α/β-amyrin with benznidazole displayed synergistic effects against amastigotes and antagonistic effects on LLCMK 2 cells. The antiamastigote activities, chemical derivatization, drug combinations and action mechanisms revealed to be crucial approaches toward this chronic disease.
Bufotenin (5-hydroxy-N,N-dimetyltryptamine) is a tryptamine alkaloid widely spread among anuran families as a component of their chemical defense system, acting as a potent hallucinogenic factor, showing similar activity to LSD upon interaction with the 5HT2 human receptor. This work demonstrates the presence of bufotenin in the skin secretion of three arboreal amphibian species of the Osteocephalus genus (Osteocephalus taurinus, Osteocephalus oophagus and Osteocephalus langsdorffii) from the Amazon and the Atlantic rain forests using RP-HPLC, ESI-MS/MS, UV, IR and multidimensional NMR techniques. To our knowledge, this is the first description of bufotenin in the Osteocephalus genus, so far.
Por meio de técnicas cromatográficas, um novo peptídeo aniônico, denominado otacidina, foi isolado das secreções cutâneas de três anuros brasileiros Osteocephalus taurinus. O sequenciamento de novo dos aminoácidos foi realizado por meio de análises por espectrometria de massas por tempo de vôo acoplada à ionização dessortiva de matriz por laser (MALDI-TOF-MS/MS). O potencial antimicrobiano deste novo metabólito foi avaliado contra cepas de Escherichia coli e Pseudomonas aeruginosa, sendo observadas concentrações inibitórias mínimas (MICs) de 37,4 e 78,4 mM, respectivamente. Este trabalho é apenas o segundo relato de um peptídeo aniônico com propriedades antimicrobianas, isolado da pele de um anfíbio.By means of chromatographic techniques, a novel anionic peptide, named otacidin, was isolated from the skin secretions of tree Brazilian anurans Osteocephalus taurinus. The de novo sequencing of the amino acids was performed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS/MS) analyses. The antimicrobial potential of this novel metabolite was evaluated against Escherichia coli and Pseudomonas aeruginosa, being observed minimum inhibitory concentration (MICs) of 37.4 and 78.4 mM, respectively. This work is just the second report of an antimicrobial anionic peptide from an amphibian.
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