Skip Navigation



JAC Advance Access published online on October 8, 2002
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkf188
© 2002 by The British Society for Antimicrobial Chemotherapy
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
50/5/629    most recent
dkf188v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by de Souza, A. O.
Right arrow Articles by Durán, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by de Souza, A. O.
Right arrow Articles by Durán, N.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2002 The British Society for Antimicrobial Chemotherapy

Original Paper

3-[4'-Bromo-(1,1'-biphenyl)-4-yl]-N,N-dimethyl-3-(2-thienyl)-2-propen-1-amine: synthesis, cytotoxicity, and leishmanicidal, trypanocidal and antimycobacterial activities

Ana O. de Souza 1, Fernando P. Hemerly 2, Adriana C. Busollo 3, Patrícia S. Melo 4, Gérzia M. C. Machado 5, Cristiana C. Miranda 5, Ricardo M. Santa-Rita 6, Marcela Haun 4, Leonor L. Leon 5, Daisy N. Sato 3, Solange L. de Castro 6, Nelson Durán 7*

1 Instituto de Química, Biological Chemistry Laboratory, Universidade Estadual de Campinas, Campinas, C.P. 6154, CEP 13083-970, SP; Department of Biochemistry and Immunology, Faculdade de Medicina de Ribeirão, Universidade de São Paulo, Ribeirão Preto, SP
2 Instituto de Química, Biological Chemistry Laboratory, Universidade Estadual de Campinas, Campinas, C.P. 6154, CEP 13083-970, SP
3 Instituto Adolfo Lutz, Ribeirão Preto, SP
4 Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP
5 Department of Immunology, IOC, Fundação Oswaldo Cruz, RJ
6 Department of Ultra-structure and Cellular Biology, IOC, Fundação Oswaldo Cruz, RJ
7 Instituto de Química, Biological Chemistry Laboratory, Universidade Estadual de Campinas, Campinas, C.P. 6154, CEP 13083-970, SP; NCA, Univesidade de Mogi das Cruzes, Mogi das Cruzes, SP, Brazil

* Corresponding author. E-mail: duran{at}iqm.unicamp.br.

Received 6 August 2001 ; revised 10 May 2002 ; accepted 25 July 2002

Abstract Current therapies for Chagas' disease, leishmaniasis and tuberculosis are unsatisfactory because of the failure rates, significant toxicity and/or drug resistance. In this study, the compound 3-[4'-bromo-(1,1'-biphenyl)-4-yl]-N,N-dimethyl-3-(2-thienyl)-2-propen-1-amine (IV) was synthesized and its trypanocidal, leishmanicidal and antimycobacterial activities were investigated. The cytotoxicity was determined on V79 cells with three endpoints: nucleic acid content, 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide reduction and Neutral Red uptake. This compound was active against different species of mycobacteria and different life cycle stages of Trypanosoma cruzi. In experiments with trypomastigotes performed at 4°C in the presence of blood, the activity was 8.8-fold more active than the standard drug, Crystal Violet. Higher activity was achieved against Leishmania amazonensis, with an ED50/24 h of 3.0 ± 0.3 µmol/L. The effect against trypanosomatids, which suggests high activity of compound IV against promastigotes of L. amazonensis and amastigotes of T. cruzi, stimulated further studies in vitro with amastigotes interiorized in macrophages and with in vivo models. Our results indicate that mammalian V79 cells are less susceptible to the action of compound IV than promastigotes of L. amazonensis (8.0-13.3-fold) and axenic amastigotes of T. cruzi (3.5-5.9-fold).


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.