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.
Highlights
Chagas disease, known as American trypanosomiasis or South American trypanosomiasis, is a protozoan disease caused by the haemoflagellate parasite Trypanosoma cruzi [1]
these N-hydroxytriarylimidazole (TAI) derivatives 3–12 were obtained, in yields varying from 20–70%, after condensation of 15 with the corresponding benzaldehydes in the presence of ammonium acetate [27]
Spectra and mass spectra of the synthesised compounds 3–12 were consistent with the proposed structures, which was corroborated by X-ray crystallography of the p-bromo-TAI derivative 6
Summary
Known as American trypanosomiasis or South American trypanosomiasis, is a protozoan disease caused by the haemoflagellate parasite Trypanosoma cruzi [1]. It is a chronic and debilitating parasitic infection that affects millions of people in Mexico, Central America, and South. The available drug for the clinical treatment of Chagas disease is the nitroheterocyclic drug benznidazole [3] This drug is effective against the circulating form of the parasite (trypomastigotes) in the acute phase of the disease, but its efficacy during the chronic stage is debatable [4]. Despite its noteworthy trypanocidal activity, megazol development was discontinued due to reports of its in vitro mutagenic and genotoxic effects [10–12]. To circumvent this undesirable profile, there have been numerous efforts to obtain megazol analogues [13–17]
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