A series of quinoline-3-carboxylic acid derivatives has been synthesized with easy reaction conditions (in aqueous micellar microreactors and using microwave irradiation) and tested for its biological activity against human African trypanosomiasis (HAT). From this series, several derivatives of quinoline-3-carboxylic acid such as 23 and 24 exhibited potent activity against Trypanosoma brucei in vitro and had low cytotoxicity. The combination of electron withdrawing and donating groups in the structure seems to be the crucial factor to inhibit T. brucei.