title: Antileishmanial activity of 5-methyl-2,2' : 5',2″-terthiophene isolated from Porophyllum ruderale is related to mitochondrial dysfunction in Leishmania amazonensis.
abstract: 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.
authors: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brazil.
authors: Helena Teru
authors: HT
authors: Takahashi
authors: Elizandra Aparecida
authors: EA
authors: Britta
authors: Renata
authors: R
authors: Longhini
authors: Tânia
authors: T
authors: Ueda-Nakamura
authors: João Carlos
authors: JC
authors: Palazzo de Mello
authors: Celso Vataru
authors: CV
authors: Nakamura
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000302:isolation & purification* / Q000494:pharmacology; D019659:Asteraceae / Q000737:chemistry*; D005434:Flow Cytometry; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007891:Leishmania / Q000187:drug effects* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D051336:Mitochondrial Membranes / Q000187:drug effects*; D013876:Thiophenes / Q000302:isolation & purification* / Q000494:pharmacology; D018675:Toxicity Tests
chemical_list: C585556:5-methyl-2,2'-5',2''-terthiophene; D000981:Antiprotozoal Agents; D013876:Thiophenes