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 IC50 values of 8.5 and 1.35 μM, respectively. Against T. b. rhodesiense, 7e was found to be the most active with an IC50 value of 1.13 μM. All synthesized active analogues were found to be non-cytotoxic against MRC-5 and PMM with selectivity indices of up to more than 50.
Keywords: Trypanosoma brucei brucei; Trypanosoma brucei rhodesiense; antikinetoplastid; chalcone; drug likeliness properties; imidazo[1,2-a]pyridine; neglected tropical diseases (NTDs).
© 2023 The Authors. Chemical Biology & Drug Design published by John Wiley & Sons Ltd.