Synthesis of Pyrazolyl Acrylamide-Chalcone Conjugates with Sub-Micromolar Antitrypanosomal Activities

A series of compounds was synthesized in 4-5 steps and studied for their activity against Trypanosoma brucei, the causative agent of human African trypanosomiasis. These compounds were also evaluated for their cytotoxicity against the HEK293 human embryonic kidney cell line. Among the synthesized analogues, 5m (R = 3-pyridyl) was the most active with an EC ₅₀ value of 0.245 ± 0.067 µM against T. brucei , but was also cytotoxic with a CC ₅₀ value of 0.285 ± 0.062 µM. Compounds 5g (R = 4-ClC ₆ H ₄ ), 5i (R = 3-NO ₂ C ₆ H ₄ ) and 5j (R = 4- NO ₂ C ₆ H ₄ ) were also active with similar EC ₅₀ values of 0.278 ± 0.081, 0.256 ± 0.043 and 0.268 ± 0.061 µM, respectively. Interestingly, the same three compounds were apparently not cytotoxic to human HEK293 cells with CC ₅₀ values >20 µM.