Synthesis and trypanocidal activity of novel 2,4,5-triaryl-N-hydroxylimidazole derivatives

• Published in: Molecules (Basel, Switzerland) Switzerland), 2013-03, Vol.18 (3), p.3445-3457
• Main Authors: da Silva, Ramon Borges, Loback, Vanessa Brandão, Salomão, Kelly, de Castro, Solange Lisboa, Wardell, James L, Wardell, Solange M S V, Costa, Thadeu Estevam Moreira Maramaldo, Penido, Carmen, Henriques, Maria das Graças Muller de Oliveira, Carvalho, Samir Aquino, da Silva, Edson Ferreira, Fraga, Carlos Alberto Manssour
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Cell Survival - drug effects; Drug Evaluation, Preclinical; Hydrazones - chemistry; Imidazoles - chemical synthesis; Imidazoles - pharmacology; Mice; Models, Molecular; Molecular Conformation; Trypanocidal Agents - chemical synthesis; Trypanocidal Agents - pharmacology; Trypanosoma cruzi - drug effects
• ISSN: 1420-3049
• DOI: 10.3390/molecules18033445

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.