In vitro and in vivo activity of the chloroaryl-substituted imidazole viniconazole against Trypanosoma cruzi

被引:4
作者
Da Silva, Cristiane Franca [1 ]
Jaen Batista, Denise Da Gama [1 ]
Batista, Marcos Meuser [1 ]
Lionel, Jessica [1 ]
Hammer, Erica Ripoll [1 ]
Brun, Reto [2 ]
Correia Soeiro, Maria De Nazare [1 ]
机构
[1] Oswaldo Cruz Fiocruz, Celular Inst, Lab Biol, Rio De Janeiro, Brazil
[2] Swiss Trop & Publ Hlth Inst, Dept Med Parasitol & Infect Biol, Basel, Switzerland
关键词
in vitro; chloroaryl-substituted imidazole; Trypanosoma cruzi; viniconazole; experimental chemotherapy; Chagas disease; in vivo; PROTOZOAN NEGLECTED DISEASES; SECONDARY METABOLITES; CHAGAS-DISEASE; PLANTS; DRUGS; LEADS;
D O I
10.1017/S0031182013001601
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
Chagas disease (CD) is caused by the intracellular protozoan parasite Trypanosoma cruzi and affects more than 10 million people in poor areas of Latin America. There is an urgent need for alternative drugs with better safety, broader efficacy, lower costs and shorter time of administration. Thus the biological activity of viniconazole, a chloroaryl-substituted imidazole was investigated using in vitro and in vivo screening models of T. cruzi infection. Ultrastructural findings demonstrated that the most frequent cellular damage was associated with plasma membrane (blebs and shedding events), Golgi (swelling aspects) and the appearance of large numbers of vacuoles suggesting an autophagic process. Our data demonstrated that although this compound is effective against bloodstream and intracellular forms (16 and 24 mu m, respectively) in vitro, it does not present in vivo efficacy. Due to the urgent need for novel agents against T. cruzi, the screening of natural and synthetic products must be further supported with the aim of finding more selective and affordable drugs for CD.
引用
收藏
页码:367 / 373
页数:7
相关论文
共 19 条
  • [1] NATURAL SESQUITERPENE LACTONES ARE ACTIVE AGAINST LEISHMANIA MEXICANA
    Barrera, Patricia A.
    Jimenez-Ortiz, Veronica
    Tonn, Carlos
    Giordano, Oscar
    Galanti, Norbel
    Sosa, Miguel A.
    [J]. JOURNAL OF PARASITOLOGY, 2008, 94 (05) : 1143 - 1149
  • [2] Batista DGJ, 2012, PLOS ONE, V7, DOI DOI 10.1371/J0URNAL.P0NE.0030356
  • [3] BRENER Z., 1962, REV INST MED TROP SAO PAULO, V4, P389
  • [4] In Vitro and In Vivo Studies of the Antiparasitic Activity of Sterol 14α-Demethylase (CYP51) Inhibitor VNI against Drug-Resistant Strains of Trypanosoma cruzi
    Correia Soeiro, Maria de Nazare
    de Souza, Elen Mello
    da Silva, Cristiane Franca
    Jaen Batista, Denise da Gama
    Batista, Marcos Meuser
    Pavao, Beatriz Philot
    Araujo, Julianna Siciliano
    Fortes Aiub, Claudia Alessandra
    da Silva, Patricia Bernardino
    Lionel, Jessica
    Britto, Constanca
    Kim, Kwangho
    Sulikowski, Gary
    Hargrove, Tatiana Y.
    Waterman, Michael R.
    Lepesheva, Galina I.
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2013, 57 (09) : 4151 - 4163
  • [5] In vitro and in vivo studies of the trypanocidal activity of a diarylthiophene diamidine against Trypanosoma cruzi
    da Silva, Cristiane Franca
    Batista, Marcos Meuser
    Jaen Batista, Denise da Gama
    de Souza, Elen Mello
    da Silva, Patricia Bernardino
    de Oliveira, Gabriel Melo
    Meuser, Andrea Souza
    Shareef, Abdur-Rafay
    Boykin, David W.
    Soeiro, Maria de Nazare C.
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2008, 52 (09) : 3307 - 3314
  • [6] Phenyl substitution of furamidine markedly potentiates its anti-parasitic activity against Trypanosoma cruzi and Leishmania amazonensis
    de Souza, EM
    Lansiaux, A
    Bailly, C
    Wilson, WD
    Hu, Q
    Boykin, DW
    Batista, MM
    Araújo-Jorge, TC
    Soeiro, MNC
    [J]. BIOCHEMICAL PHARMACOLOGY, 2004, 68 (04) : 593 - 600
  • [7] CYP51 structures and structure-based development of novel, pathogen-specific inhibitory scaffolds
    Hargrove, Tatiana Y.
    Kim, Kwangho
    Correia Soeiro, Maria de Nazare
    da Silva, Cristiane Franca
    Jaen Batista, Denise da Gama
    Batista, Marcos Meuser
    Yazlovitskaya, Eugenia M.
    Waterman, Michael R.
    Sulikowski, Gary A.
    Lepesheva, Galina I.
    [J]. INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE, 2012, 2 : 178 - 186
  • [8] Combined Treatment of Heterocyclic Analogues and Benznidazole upon Trypanosoma cruzi In Vivo
    Jaen Batista, Denise da Gama
    Batista, Marcos Meuser
    de Oliveira, Gabriel Melo
    Britto, Constanca Carvalho
    Mondaine Rodrigues, Ana Carolina
    Stephens, Chad E.
    Boykin, David W.
    Correia Soeiro, Maria de Nazare
    [J]. PLOS ONE, 2011, 6 (07):
  • [9] Arylimidamide DB766, a Potential Chemotherapeutic Candidate for Chagas' Disease Treatment
    Jaen Batista, Denise da Gama
    Batista, Marcos Meuser
    de Oliveira, Gabriel Melo
    do Amaral, Patricia Borges
    Lannes-Vieira, Joseli
    Britto, Constanca Carvalho
    Junqueira, Angela
    Lima, Marli Maria
    Romanha, Alvaro Jose
    Sales Junior, Policarpo Ademar
    Stephens, Chad E.
    Boykin, David W.
    Correia Soeiro, Maria de Nazare
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2010, 54 (07) : 2940 - 2952
  • [10] Mortality due to Chagas disease in Brazil from 1979 to 2009: trends and regional differences
    Martins-Melo, Francisco Rogerlandio
    Ramos, Alberto Novaes, Jr.
    Alencar, Carlos Henrique
    Heukelbach, Jorg
    [J]. JOURNAL OF INFECTION IN DEVELOPING COUNTRIES, 2012, 6 (11): : 817 - 824