title: Synthesis and trypanocidal activity of novel 2,4,5-triaryl-N-hydroxylimidazole derivatives.
abstract: Herein, we report the design, synthesis and trypanocidal activity of some novel trisubstituted imidazole derivatives. These heterocyclic derivatives were structurally planned by exploring the concept of molecular hybridisation between two arylhydrazones derived from megazol, which has potent trypanocidal activity. The trypanocidal activity of these triarylimidazole derivatives was evaluated against infective trypomastigote forms of T. cruzi and the derivative 2'-(4-bromophenyl)-1-methyl-5'-phenyl-1H,3'H-2,4'-biimidazol-3'-ol showed moderate biological activity (IC50 = 23.9 µM) when compared to benznidazole, a standard trypanocidal drug. These compounds did not present cytotoxic effects at concentrations near the trypanocidal IC50, being considered a good starting point for the development of new anti-Chagas drug candidates.
authors.affiliation: Instituto de Tecnologia em Fármacos - Farmanguinhos, Fundação Oswaldo Cruz, 21041-250, Rio de Janeiro, RJ, Brazil. ramonpan@ig.com.br
authors.forename: Ramon Borges
authors.initials: RB
authors.lastname: da Silva
authors.forename: Vanessa Brandão
authors.initials: VB
authors.lastname: Loback
authors.forename: Kelly
authors.initials: K
authors.lastname: Salomão
authors.forename: Solange Lisboa
authors.initials: SL
authors.lastname: de Castro
authors.forename: James L
authors.initials: JL
authors.lastname: Wardell
authors.forename: Solange M S V
authors.initials: SM
authors.lastname: Wardell
authors.forename: Thadeu Estevam Moreira Maramaldo
authors.initials: TE
authors.lastname: Costa
authors.forename: Carmen
authors.initials: C
authors.lastname: Penido
authors.forename: Maria das Graças Muller de Oliveira
authors.initials: Md
authors.lastname: Henriques
authors.forename: Samir Aquino
authors.initials: SA
authors.lastname: Carvalho
authors.forename: Edson Ferreira
authors.initials: EF
authors.lastname: da Silva
authors.forename: Carlos Alberto Manssour
authors.initials: CA
authors.lastname: Fraga
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006835:Hydrazones / Q000737:chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D006835:Hydrazones; D007093:Imidazoles; D014344:Trypanocidal Agents