title: Activity of "reversed" diamidines against Trypanosoma cruzi "in vitro".
abstract: Chagas' disease is an important parasitic illness caused by the flagellated protozoan Trypanosoma cruzi. The disease affects nearly 17 million individuals in endemic areas of Latin America and the current chemotherapy is quite unsatisfactory based on nitroheterocyclic agents (nifurtimox and benznidazol). The need for new compounds with different modes of action is clear. Due to the broad-spectrum antimicrobial activity of the aromatic dicationic compounds, this study focused on the activity of four such diamidines (DB811, DB889, DB786, DB702) and a closely related diguanidine (DB711) against bloodstream trypomastigotes as well as intracellular amastigotes of T. cruzi in vitro. Additional studies were also conducted to access the toxicity of the compounds against mammalian cells in vitro. Our data show that the four diamidines compounds presented early and high anti-parasitic activity (IC50 in low-micromolecular range) exhibiting trypanocidal dose-dependent effects against both trypomastigote and amastigote forms of T. cruzi 2h after drug treatment. Most of the diamidines compounds (except the DB702) exerted high anti-parasitic activity and low toxicity to the mammalian cells. Our results show the activity of reversed diamidines against T. cruzi and suggested that the compounds merit in vivo studies.
authors.affiliation: Lab. Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: C F
authors.initials: CF
authors.lastname: Silva
authors.forename: Marcos Meuser
authors.initials: MM
authors.lastname: Batista
authors.forename: Renata Alves
authors.initials: RA
authors.lastname: Mota
authors.forename: Elen Mello
authors.initials: EM
authors.lastname: de Souza
authors.forename: Chad E
authors.initials: CE
authors.lastname: Stephens
authors.forename: Phanneth
authors.initials: P
authors.lastname: Som
authors.forename: David Wilson
authors.initials: DW
authors.lastname: Boykin
authors.forename: Maria de Nazaré C
authors.initials: Mde N
authors.lastname: Soeiro
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology; D019791:Guanidine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008018:Life Cycle Stages / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects; D015394:Molecular Structure; D010419:Pentamidine / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development*; D014709:Vero Cells
chemical_list: D005663:Furans; D014344:Trypanocidal Agents; C520808:diguanidine; D010419:Pentamidine; D019791:Guanidine