In vitro trypanocidal activity of DB745B and other novel arylimidamides against Trypanosoma cruzi

• Published in: Journal of antimicrobial chemotherapy Vol. 66; no. 6; pp. 1295 - 1297
• Main Authors: FRANCA DA SILVA, Cristiane, JUNQUEIRA, Angela, LIMA, Marli Maria, JOSE ROMANHA, Alvaro, ADEMAR SALES JUNIOR, Policarpo, STEPHENS, Chad E, SOM, Phanneth, BOYKIN, David W, DE NAZARE CORREIA SOEIRO, Maria
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-06-2011; Oxford Publishing Limited (England)
• Subjects: Amidines - pharmacology; Amidines - toxicity; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - toxicity; Biological and medical sciences; Cardiomyocytes; Cell Survival - drug effects; Cells, Cultured; Human protozoal diseases; Humans; Infectious diseases; Inhibitory Concentration 50; Medical sciences; Mice; Microscopy; Myocytes, Cardiac - drug effects; Parasites; Parasitic diseases; Parasitic Sensitivity Tests; Pharmacology. Drug treatments; Protozoal diseases; Rodents; Tetrazolium Salts - metabolism; Thiazoles - metabolism; Toxicity; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Trypanosomiasis; Kinetoplastida; Protozoa; Protozoal disease; Chagas disease; T. cruzi; Parasitosis; In vitro; Biological activity; Trypanosoma cruzi; Infection; Chemotherapy; Treatment; Chagas' disease; Trypanosomiasis
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkr140

As part of a search for new therapeutic opportunities to treat chagasic patients, in vitro efficacy studies were performed to characterize the activity of five novel arylimidamides (AIAs) against Trypanosoma cruzi.
The trypanocidal effect against T. cruzi was evaluated by light microscopy through the determination of IC₅₀ values. Cytotoxicity was determined by MTT assays against mouse cardiomyocytes.
Our data demonstrated the trypanocidal efficacy of these new compounds against bloodstream trypomastigotes and intracellular amastigotes, exhibiting IC₅₀ values ranging from 0.015 to 2.5 and 0.02 to0.2 μM, respectively. One of the compounds, DB745B, was also highly active against a broad panel of isolates, including those naturally resistant to benznidazole. DB745B showed higher in vitro efficacy than the reference drugs used to treat patients (benznidazole IC₅₀= 12.94 μM) and to prevent blood bank infection (gentian violet IC₅₀= 30.6 μM).
AIAs represent promising new chemical entities against T. cruzi and are also potential trypanocidal agents to prevent transfusion-associated Chagas' disease.