Characterization and Trypanocidal Activity of a Novel Pyranaphthoquinone.

Chagas disease is an endemic parasitic infection that occurs in 21 Latin American countries. New therapies for this disease are urgently needed, as the only two drugs available (nifurtimox and benznidazol) have high toxicity and variable efficacy in the disease's chronic phase. Recently, a new chemical entity (NCE) named Pyranaphthoquinone (IVS320) was synthesized from lawsone. We report herein, a detailed study of the physicochemical properties and in vitro trypanocidal activity of IVS320. A series of assays were performed for characterization, where thermal, diffractometric, and morphological analysis were performed. In addition, the solubility, permeability, and hygroscopicity of IVS320 were determined. The results show that its poor solubility and low permeability may be due to its high degree of crystallinity (99.19%), which might require the use of proper techniques to increase the IVS320's aqueous solubility and permeability. The trypanocidal activity study demonstrated that IVS320 is more potent than the reference drug benznidazole, with IC50/24 h of 1.49 ± 0.1 µM, which indicates that IVS320 has potential as a new drug candidate for the treatment of Chagas disease.

Connarus favosus Planch.: An inhibitor of the hemorrhagic activity of Bothrops atrox venom and a potential antioxidant and antibacterial agent.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant species Connarus favosus is used in folk medicine in the west of Pará state, Brazil, to treat snakebites. AIM OF THE STUDY: To investigate the potential of the aqueous extract of Connarus favosus (AECf) to inhibit hemorrhagic and phospholipase A2 activities induced by Bothrops atrox venom (BaV) and to determine the antioxidant and antimicrobial potentials of the extract. MATERIALS AND METHODS: AECf was analyzed phytochemically for phenolics (condensed tannins and hydrolyzable tannins) by colorimetry. Antioxidant activity was evaluated by quantitative assays using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Fe(3+)/phenanthroline. Antimicrobial activity was evaluated by the minimal inhibitory concentration test, and cytotoxicity was evaluated using human fibroblast cells (MRC-5). Inhibition of BaV-induced hemorrhagic activity was assessed after oral administration of the extract using pre-treatment, post-treatment and combined (BA plus AECf) treatment protocols. Inhibition of indirect hemolysis caused by phospholipase A2 (PLA2) was investigated in vitro. Interaction between AECf and BaV was investigated by SDS-PAGE electrophoresis, Western blot (Wb) and zymography. RESULTS: The phytochemical profile of AECf revealed ten secondary metabolite classes, and colorimetry showed high total phenolic and total (condensed and hydrolyzable) tannin content. AECf exhibited high antioxidant and antimicrobial potentials. The IC50 for the cytotoxic effect was 51.91 (46.86-57.50)µg/mL. Inhibition of BaV-induced hemorrhagic activity was significant in all the protocols, and inhibition of PLA2 activity was significant with the two highest concentrations. The BaV/AECf mixture produced the same bands as BaV by itself in SDS-PAGE and Wb although the bands were much fainter. Zymography confirmed the proteolytic activity of BaV, but when the venom was pre-incubated with AECf this activity was blocked. CONCLUSION: AECf was effective in reducing BaV-induced hemorrhagic activity when administered by the same route as that used in folk medicine and exhibited antioxidant and antimicrobial potentials.