a1 Laboratório de Biologia Celular, Maria de Nazaré Correia Soeiro, Av. Brasil, 4365. Manguinhos, Rio de Janeiro, RJ, Brazil
a2 Department of Chemistry, Augusta State University, Augusta, Georgia, USA
a3 Department of Chemistry and Physics, Augusta State University, Augusta, Georgia, USA
The present study aimed to determine the in vitro biological efficacy and selectivity of 7 novel AIAs upon bloodstream trypomastigotes and intracellular amastigotes of Trypanosoma cruzi. The biological activity of these aromatic compounds was assayed for 48 and 24 h against intracellular parasites and bloodstream forms of T. cruzi (Y strain), respectively. Additional assays were also performed to determine their potential use in blood banks by treating the bloodstream parasites with the compounds diluted in mouse blood for 24 h at 4°C. Toxicity against mammalian cells was evaluated using primary cultures of cardiac cells incubated for 24 and 48 h with the AIAs and then cellular death rates were determined by MTT colorimetric assays. Our data demonstrated the outstanding trypanocidal effect of AIAs against T. cruzi, especially DB1853, DB1862, DB1867 and DB1868, giving IC50 values ranging between 16 and 70 nanomolar against both parasite forms. All AIAs presented superior efficacy to benznidazole and some, such as DB1868, also demonstrated promising activity as a candidate agent for blood prophylaxis. The excellent anti-trypanosomal efficacy of these novel AIAs against T. cruzi stimulates further in vivo studies and justifies the screening of new analogues with the goal of establishing a useful alternative therapy for Chagas disease.
(Received June 20 2011)
(Revised July 27 2011)
(Accepted July 28 2011)
(Online publication September 09 2011)
c1 Corresponding author: Laboratório de Biologia Celular, Maria de Nazaré Correia Soeiro, Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, Brazil. Tel: +055 21 25621368. Fax: +055 21 2562-1432. E-mail: [email protected]
† Both authors contributed equally to this study.