Pyrazolyl amide-chalcones conjugates: Synthesis and antikinetoplastid activity

A series of novel pyrazolyl amide-chalcones conjugates was synthesized in five steps and evaluated against a range of medically important kinetoplastid parasites including Trypanosoma cruzi, Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense and Leishmania infantum. In addition, the series was also tested for in vitro cytotoxicity activity against human lung fibroblasts and primary mouse macrophages. Among all synthetised compounds, 9b was found to be the most active against T. b. brucei with an IC₅₀ value of 0.51 ± 0.06 μM. Against T. b. rhodesiense, 9n was found to be the most potent with an IC₅₀ value of 0.46 ± 0.07 μM. While against L. infantum, 9a was found to be most active with an IC₅₀ value of 7.16 ± 1.88 μM. Based on the results and SAR, further modifications will be carried out to increase potency.