title: The efficacy of novel arylimidamides against Trypanosoma cruzi in vitro.
abstract: 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.
authors: Laboratório de Biologia Celular, Maria de Nazaré Correia Soeiro, Av. Brasil, 4365. Manguinhos, Rio de Janeiro, RJ, Brazil.
authors: Cristiane França
authors: CF
authors: DA Silva
authors: Laboratório de Biologia Celular, Maria de Nazaré Correia Soeiro, Av. Brasil, 4365. Manguinhos, Rio de Janeiro, RJ, Brazil.
authors: Anissa
authors: A
authors: Daliry
authors: Laboratório de Biologia Celular, Maria de Nazaré Correia Soeiro, Av. Brasil, 4365. Manguinhos, Rio de Janeiro, RJ, Brazil.
authors: Patrícia Bernardino
authors: PB
authors: DA Silva
authors: Department of Chemistry, Augusta State University, Augusta, Georgia, USA.
authors: Senol
authors: S
authors: Akay
authors: Department of Chemistry, Augusta State University, Augusta, Georgia, USA.
authors: Moloy
authors: M
authors: Banerjee
authors: Department of Chemistry, Augusta State University, Augusta, Georgia, USA.
authors: Abdelbasset A
authors: AA
authors: Farahat
authors: Department of Chemistry and Physics, Augusta State University, Augusta, Georgia, USA.
authors: Mary K
authors: MK
authors: Fisher
authors: Department of Chemistry, Augusta State University, Augusta, Georgia, USA.
authors: Laixing
authors: L
authors: Hu
authors: Department of Chemistry, Augusta State University, Augusta, Georgia, USA.
authors: Arvind
authors: A
authors: Kumar
authors: Department of Chemistry, Augusta State University, Augusta, Georgia, USA.
authors: Zongying
authors: Z
authors: Liu
authors: Department of Chemistry and Physics, Augusta State University, Augusta, Georgia, USA.
authors: Chad E
authors: CE
authors: Stephens
authors: Department of Chemistry, Augusta State University, Augusta, Georgia, USA.
authors: David W
authors: DW
authors: Boykin
authors: Laboratório de Biologia Celular, Maria de Nazaré Correia Soeiro, Av. Brasil, 4365. Manguinhos, Rio de Janeiro, RJ, Brazil.
authors: Maria D E Nazaré
authors: MD
authors: Correia Soeiro
mesh_terms: D000577:Amides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D020128:Inhibitory Concentration 50; D051379:Mice; D032383:Myocytes, Cardiac; D009593:Nitroimidazoles / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000577:Amides; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C009999:benzonidazole