Fome e Abundância: Um Paradoxo Brasileiro?
17 a 22 de outubro de 2016
Trabalho 6782
| ISSN | 2237-9045 |
|---|---|
| Instituição | Universidade Federal de Viçosa |
| Nível | Pós-graduação |
| Modalidade | Pesquisa |
| Área de conhecimento | Ciências Biológicas e da Saúde |
| Área temática | Farmacologia e bioquímica |
| Setor | Departamento de Bioquímica e Biologia Molecular |
| Bolsa | Outros |
| Conclusão de bolsa | Não |
| Apoio financeiro | Outros |
| Primeiro autor | Luciana Ângelo de Souza |
| Orientador | JULIANA LOPES RANGEL FIETTO |
| Outros membros | Joice de Melo Agripino, Matheus Silva e Bastos, Raymond J.Pierce, Wolfgang Sippl |
| Título | Furamidine leishmanicidal activity in Leishmania braziliensis |
| Resumo | Leishmaniasis is a spectrum of neglected tropical diseases affecting people around the world, with 1.3 million new cases each year and 20,000 to 30,000 deaths in the same period. Leishmaniasis is caused by infection of the vertebrate host to one of over 20 different species of protozoan parasites of the genus Leishmania, transmitted through the bite of female sand flies during its blood meal. Leishmania braziliensis is the main species responsible for cutaneous leishmaniasis in the New World and Brazil is the country with the highest incidence of disease in South America. The treatment for the various forms of leishmaniasis in humans depends today, and mainly, on chemotherapy, as there is no effective and licensed vaccine against the disease. The drugs used in the treatment of leishmaniasis cause many and serious side effects, and in addition, the parasites have shown resistance to these drugs. In this scenario, this work is part of an effort of several national and international institutions, financed by the European Community by the consortium A-ParaDDisE (http:a-paraddise.cebio.org/), whose objective is the discovery of new drugs for the treatment of neglected parasitic diseases, based on epigenetic targets. Histone modifying enzymes (HMEs) are enzymes responsible for post-translational modifications of histone tails on DNA, and these modifications are responsible for gene activation or repression. These enzymes are highly conserved in eukaryotes and essential for the survival of some parasites. HME inhibitors have been studied as candidate drugs for use in the chemotherapy of a variety of diseases, including cancer and parasitic diseases since they inhibit cell cycle progression and/or induce apoptosis. Furamidine is an aromatic diamidine able to inhibit protein arginine methyltransferases (PRMT), HMEs involved in histone methylation processes. Furthermore, furamidine has proven effective against some parasites such as //Plasmodium falciparum// and Trypanosoma rhodesiense. The objective of this study was to evaluate the action of furamidine in axenic promastigotes and intracellular amastigotes of L. braziliensis and also in a model host cell, Raw 264.7 macrophages. Tests were performed in 96 well plates and the action of the compounds was assessed by fluorescence and the resazurin method after 48 hours. The results show that in L. braziliensis axenic promastigotes, even the highest concentration of furamidine used, 50μM was able to inhibit only 30% of the growth of parasites. In infection assays, this same concentration was able to inhibit 100% of the growth of intracellular amastigotes compared to amphotericin B, the drug used as a positive control. At concentrations of 10 µM and 2 µM , furamidine was able to inhibit intracellular amastigotes growth by 82% and 49%, respectively. For macrophages, a 50 µM concentration was toxic, inhibiting more than 60% cell growth, indicating a therapeutic index of 5-20 in the in vitro// assay. |
| Palavras-chave | Leishmania braziliensis, furamidine, histone modifying enzymes |
| Forma de apresentação..... | Painel |