Antileishmanial Activity of 5-Methyl-2,2′ : 5′,2″-terthiophene
                    Isolated from Porophyllum ruderale is Related to Mitochondrial
                    Dysfunction in Leishmania amazonensis

Helena Teru Takahashi; Elizandra Aparecida Britta; Renata Longhini; Tânia Ueda-Nakamura; João Carlos Palazzo de Mello; Celso Vataru Nakamura

doi:10.1055/s-0032-1328258

Planta Medica, Inhaltsverzeichnis

Planta Med 2013; 79(05): 330-333
DOI: 10.1055/s-0032-1328258

Biological and Pharmacological Activity

Letters

Georg Thieme Verlag KG Stuttgart · New York

Antileishmanial Activity of 5-Methyl-2,2′ : 5′,2″-terthiophene Isolated from Porophyllum ruderale is Related to Mitochondrial Dysfunction in Leishmania amazonensis

Helena Teru Takahashi

¹Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brazil

,

Elizandra Aparecida Britta

¹Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brazil

,

Renata Longhini

¹Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brazil

,

Tânia Ueda-Nakamura

¹Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brazil

²Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Maringá, PR, Brazil

,

João Carlos Palazzo de Mello

¹Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brazil

³Departamento de Farmácia, Universidade Estadual de Maringá, Maringá, PR, Brazil

,

Celso Vataru Nakamura

¹Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brazil

²Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Maringá, PR, Brazil

› Institutsangaben

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.

Key words

Porophyllum ruderale - Asteraceae - thiophene derivatives - mitochondrion dysfunction

Volltext

Referenzen

References
1 Desjeux P. Leishmaniasis: public health aspects and control. Clin Dermatol 1996; 14: 417-423
2 Tiuman TS, Santos AO, Ueda-Nakamura T, Dias Filho BP, Nakamura CV. Recent advances in leishmaniasis treatment. Int J Infect Dis 2011; 15: 525-532
3 Crotti A, dos Santos F, Magalhães L, Wakabayashi K, Aguiar G, Carvalho C, Melo N, Veneziani R, Albuquerque S, Da Silva Filho A. Screening of selected essential oils for their in vitro antileishmanial activity against Leishmania amazonensis . Planta Med 2010; 76: 453
4 Pan L, Lezama-Davila CM, Isaac-Marquez AP, Fuchs JR, Satoskar AR, Kinghorn AD. Compounds with antileishmanial activity isolated from the stems of Pentalinon andrieuxii . Planta Med 2012; 78: PI239
5 Rojas-Silva P, Graziose R, Poulev A, Mbeunkui F, Grace MH, Lila MA, Raskin I. Seeking novel Leishmanicidal natural products from common medicinal plants, the example of Eryngium foetidum L. Planta Med 2012; 78: PF87
6 Jorge AS, Silveira TGV, Lonardoni MVC, Arraes SMAA, Zanzarini PD, Silva CM, Mello JCP, Bertolini DA. Crude extract of “cravinho” [Porophyllum ruderale (Jacq.) Cass.] show activity against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis . Mem Inst Oswaldo Cruz 1998; 93: 298
7 Takahashi HT, Novello CR, Ueda-Nakamura T, Dias Filho BP, Mello JCP, Nakamura CV. Thiophene derivatives with antileishmanial activity isolated from aerial parts of Porophyllum ruderale (Jacq.) Cass. Molecules 2011; 16: 3469-3478
8 Santos AO, Veiga-Santos P, Ueda-Nakamura T, Dias-Filho BP, Sudatti DB, Bianco EM, Pereira RC, Nakamura CV. Effect of elatol isolated from red seaweed Laurencia dendroidea on Leishmania amazonensis . Marine Drugs 2010; 8: 2733-2743
9 Van Hellemond JJ, Opperdoes FR, Tielens AG. The extraordinary mitochondrion and unusual citric acid cycle in Trypanosoma brucei . Biochem Soc Trans 2005; 33: 967-971
10 Hu L, Arafa RD, Ismail MA, Wenzler T, Brun R, Munde M, Wilson WD, Nzimiro S, Samyesudhas S, Werbovetz KA, Boykin W. Azaterphenyl diamidines as antileishmanial agents. Bioorg Med Chem Lett 2008; 18: 247-251
11 Conceição K, Konno K, Richardson M, Antoniazzi MM, Jared C, Daffre S, Camargo ACM, Pimenta DC. Isolation and biochemical characterization of peptides presenting antimicrobial activity from the skin of Phyllomedusa hypochondrialis . Peptides 2006; 27: 3092-3099
12 Santa-Rita RM, Henrique-Pons A, Barbosa HS, Castro SL. Effect of the lysophospholipid analogues edelfosine, ilmofosine and miltefosine against Leishmania amazonensis . J Antimicrob Chemother 2004; 54: 704-710
13 Fonseca-Silva F, Inacio JDF, Canto-Cavalheiro MM, Almeida-Amaral EE. Reactive oxygen species production and mitochondrial dysfunction contribute to quercetin induced death in Leishmania amazonensis . PLoS One 2011; 6: 1-7
14 Gould MK, Vu XL, Seebeck T, Koning HP. Propidium iodide-based methods for monitoring drug action in the kinetoplastidae: comparison with the Alamar Blue assay. Anal Biochem 2008; 382: 87-93
15 Tempone AG, Pimenta DC, Lebrun I, Sartorelli P, Taniwaki NN, Andrade Jr. HF, Antoniazzi MM, Jared C. Antileishmanial and antitrypanosomal activity of bufadienolides isolated from the toad Rhinella jimi parotoid macrogland secretion. Toxicon 2008; 52: 13-21

Zusatzmaterial

Supporting Information