Neolignans from plants in northeastern Brazil (Lauraceae) with activity against Trypanosoma cruzi

• Published in: Experimental parasitology 2010-03, Vol.124 (3), p.319-324
• Main Authors: Cabral, M.M.O., Barbosa-Filho, J.M., Maia, G.L.A., Chaves, M.C.O., Braga, M.V., De Souza, W., Soares, R.O.A.
• Format: Article
• Language: English
• Subjects: Animals; Benzofurans - chemistry; Benzofurans - pharmacology; Benzofurans - toxicity; Biological and medical sciences; Blood Transfusion - standards; Brazil; Burchellin; Cell Survival - drug effects; Chagas Disease - prevention & control; Chagas Disease - transmission; Chemotherapy; drug therapy; drug toxicity; epimastigotes; Fundamental and applied biological sciences. Psychology; Humans; Inhibitory Concentration 50; Lauraceae; Licarin A; Life cycle. Host-agent relationship. Pathogenesis; lignans; Lignans - chemistry; Lignans - pharmacology; Lignans - toxicity; macrophages; Macrophages, Peritoneal - cytology; Macrophages, Peritoneal - drug effects; mechanism of action; Mice; Mice, Inbred BALB C; Microscopy, Electron, Transmission; Nectandra; Nectandra glabracens; Nectandra glabrescens; Neolignans; Ocotea; Ocotea cymbarum; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Extracts - toxicity; Protozoa; Trypanocidal Agents - chemistry; Trypanocidal Agents - pharmacology; Trypanocidal Agents - toxicity; trypanocides; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Trypanosoma cruzi - growth & development; Trypanosoma cruzi - ultrastructure; trypanosomiasis; trypomastigotes; viability
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2009.11.007

Trypanosoma cruzi is the ethiological agent for Chagas disease in Latin America. This study aimed to test the trypanocidal effect of licarin A and burchellin isolated from plants in northeastern Brazil. These neolignans were tested on T. cruzi and on peritoneal macrophages, to evaluate drug toxicity. Epimastigote growth was inhibited in 45% with licarin A and 20% with burchellin with an IC 50/96 h of 462.7 μM and 756 μM, respectively. Epimastigotes treated with licarin A presented swollen mitochondria and disorganized mitochondrial cristae, kDNA and Golgi complex. When treated with burchellin, they presented enormous autophagosomes and chromatin disorganization. Licarin A and burchellin were able to induce trypomastigote death with IC 50/24 h of 960 μM and 520 μM, respectively. Although licarin A presented an IC 50 for trypomastigotes higher than for epimastigotes, both substances acted as therapeutic trypanocidal agents, because they were able to kill parasites without affecting macrophages. Due to our results, burchellin and licarin A need to be further analysed to observe if they may be used as alternative blood additive prophylaxis against Chagas disease, since it has been established that blood transfusion is an important mechanism in the transmission process.