Synthesis and biological evaluation of 2,3-dihydroimidazo[1,2-a]benzimidazole derivatives against Leishmania donovani and Trypanosoma cruzi

• HTS/HCS campaign was performed to identify anti-leishmanial and anti-Trypanosoma cruzi agents.
• 2,3-Dihydroimidazo[1,2-a]benzimidazole was a novel scaffold of anti-parasitic agents.
• Synthetic analogues were tested against intracellular and extracellular parasite forms.
• 4 and 24 showed superior anti-trypanosomal activity compared to current drug.

A high-throughput (HTS) and high-content screening (HCS) campaign of a commercial library identified 2,3-dihydroimidazo[1,2-a]benzimidazole analogues as a novel class of anti-parasitic agents. A series of synthetic derivatives were evaluated for their in vitro anti-leishmanial and anti-trypanosomal activities against Leishmania donovani and Trypanosoma cruzi, which have been known as the causative parasites for visceral leishmaniasis and Chagas disease, respectively. In the case of Leishmania, the compounds were tested in both intracellular amastigote and extracellular promastigote assays. Compounds 4 and 24 showed promising anti-leishmanial activity against intracellular L. donovani (3.05 and 5.29 μM, respectively) and anti-trypanosomal activity against T. cruzi (1.10 and 2.10 μM, respectively) without serious cytotoxicity toward THP-1 and U2OS cell lines.

2,3-Dihydroimidazo[1,2-a]benzimidazole derivatives were synthesized and evaluated against Leishmania donovani and Trypanosoma cruzi.Figure optionsDownload as PowerPoint slide