Synthesis of pyrazolyl acrylamide-chalcone conjugates with sub-micromolar antitrypanosomal activities

A series of compounds was synthesized in 3 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, compounds 5g (R = 4-ClC6H4), 5i (R = 3-NO2C6H4) and 5j (R = 4-NO2C6H4) were the most active with similar EC50 values of 0.278 ± 0.081, 0.256 ± 0.043 and 0.268 ± 0.061 µM, respectively. These hit compounds were not cytotoxic against HEK293 cells with CC50 values > 20 µM, demonstrating a selectivity index of > 100.