Design and synthesis of imidazo[1,2-a]pyridine-chalcone conjugates as antikinetoplastid agents.

A library of imidazo[1,2-a]pyridine-appended chalcones were synthesized and characterized using (1) H NMR, (13) C NMR and HRMS. The synthesized analogues were screened for their antikinetoplastid activity against Trypanosoma cruzi, Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense and Leishmania infantum. The analogues were also tested for their cytotoxicity activity against human lung fibroblasts and primary mouse macrophages. Among all screened derivatives, 7f was found to be the most active against T. cruzi and T. b. brucei exhibiting IC(50) values of 8.5 and 1.35 muM, respectively. Against T. b. rhodesiense, 7e was found to be the most active with an IC(50) value of 1.13 muM. All synthesized active analogues were found to be non-cytotoxic against MRC-5 and PMM with selectivity indices of up to more than 50.