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

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 t...

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Bibliographic Details
Published in:	Journal of antimicrobial chemotherapy Vol. 50; no. 5; pp. 629 - 637
Main Authors:	de Souza, Ana O., Hemerly, Fernando P., Busollo, Adriana C., Melo, Patrícia S., Machado, Gérzia M. C., Miranda, Cristiana C., Santa-Rita, Ricardo M., Haun, Marcela, Leon, Leonor L., Sato, Daisy N., de Castro, Solange L., Durán, Nelson
Format:	Journal Article
Language:	English
Published:	Oxford Oxford University Press 01-11-2002 Oxford Publishing Limited (England)
Subjects:	Amines - chemical synthesis Amines - pharmacology Animals Anti-Bacterial Agents - chemical synthesis Anti-Bacterial Agents - pharmacology Antibacterial agents Antibiotics. Antiinfectious agents. Antiparasitic agents Antiparasitic agents Antiprotozoal Agents - chemical synthesis Antiprotozoal Agents - pharmacology Antitubercular Agents - chemical synthesis Antitubercular Agents - pharmacology Biological and medical sciences Biphenyl Compounds - chemical synthesis Biphenyl Compounds - pharmacology Cell Survival - drug effects Cell Survival - physiology Leishmania - drug effects Leishmania - physiology Medical sciences Microbial Sensitivity Tests - statistics & numerical data Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - physiology Pharmacology. Drug treatments Trypanocidal Agents - chemical synthesis Trypanocidal Agents - pharmacology Trypanosoma cruzi - drug effects Trypanosoma cruzi - physiology Kinetoplastida Protozoa Mycobacterium Trypanosoma Drug susceptibility test Toxicity In vitro Biological activity Propene Amine Mycobacteriales Leishmania Parasiticid Mycobacteriaceae Bacteria Actinomycetes Antibacterial agent Chemical synthesis
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Summary:	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).
Bibliography:	istex:FE75DD6A6BD66C7616DB60FE11C8070A64CC21C3 Received 6 August 2001; returned 20 April 2002; revised 10 May 2002; accepted 25 July 2002 local:dkf188 ark:/67375/HXZ-W2L6PB3N-P ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0305-7453 1460-2091 1460-2091
DOI:	10.1093/jac/dkf188