Antileishmanial activity of 5-methyl-2,2' : 5',2″-terthiophene isolated from Porophyllum ruderale is related to mitochondrial dysfunction in Leishmania amazonensis.

Recently, our group isolated and reported the antiproliferative activity in promastigotes and axenic amastigote forms of Leishmania amazonensis treated with 5-methyl-2,2':5',2″-terthiophene (compound A) and 5'-methyl-[5-(4-acetoxy-1-butynyl)]-2,2'-bi-thiophene (compound B) isolated from the aerial parts of Porophyllum ruderale. Here, we demonstrated that both compounds exhibited activity against intracellular amastigotes showing IC50 values of 37 and 51 µg/mL for compounds A and B, respectively. Both compounds showed low levels of toxicity for human cells, even at the highest concentrations (hemolytic index < 10 % at 500 µg/mL). Promastigotes treated with compound A showed an alteration in the mitochondrial membrane when observed by flow cytometry through labeling with rhodamine 123 and this was confirmed by transmission electron microscopy. Alterations on morphology (rounded cells) were observed by scanning electron microscopy in parasites treated with the compounds. Further studies should be performed employing compounds A and B for the development of new drugs for chemotherapy of leishmaniasis.

Thiophene derivatives with antileishmanial activity isolated from aerial parts of Porophyllum ruderale (Jacq.) Cass.

Porophyllum ruderale (Jacq.) Cass. is a plant native to Brazil and in the northwest region of the state of Paraná, Brazil, aerial parts of P. ruderale have been used popularly in the treatment of lesions caused by Leishmania sp.. In this study the antileishmanial and cytotoxic activities of the crude extract, fractions, and isolated compounds from aerial parts of P. ruderale was evaluated. The dichloromethane extract was submitted to chromatography to yield compounds active against Leishmania amazonensis. Their structures were established by comparison of their spectroscopic data with literature values. The activities of crude extract against promastigote and axenic amastigote forms of L. amazonensis (IC(50)) were 60.3 and 77.7 µg/mL, respectively. Its cytotoxic activity against macrophage cells (CC(50)) was 500 µg/mL. The thiophene derivatives isolated were: 5-methyl-2,2':5',2"-terthiophene (compound A) and 5'-methyl-[5-(4-acetoxy-1-butynyl)]-2,2'-bithiophene (compound B). The activity of compound A against promastigote and axenic amastigote forms were 7.7 and 19.0 µg/mL and of compound B were 21.3 and 28.7 µg/mL, respectively. The activity of the isolated compounds against promastigote and axenic amastigote forms was better than that of the crude extract and more selective against protozoa than for macrophage cells.

Dengue: combatida pela prevençäo / Dengue: combated through prevention

Este artigo apresenta o trabalho realizado por alunos do Grupo Interdisciplinar e Multiprofissional GIM-3 do PEEPIN, no período de março a novembro de 1996, em integraçäo com agentes da Fundaçäo Nacional da Saúde, Unidade Básica de Saúde do Conjunto Habitacional Säo Lourenço, Conselho de Saúde da Regiäo Sul e Escola Estadual Vani César Ruiz, no combate e prevençäo do dengue na área de abrangência da UBS Säo Lourenço, na regiäo sul do Município de Londrina