Structure-activity relationships of quinoidal derivatives against Trypanosoma brucei.

Quinoidal compounds are a well-established class of redox-active molecules with recognized biological activities, including cytotoxicity and antiparasitic effects. In the context of human African trypanosomiasis (HAT), the demand for novel therapeutic options has encouraged interest in repurposing and further characterizing known compounds. In this study, a set of previously described quinoidal derivatives was evaluated for in vitro activity against Trypanosoma brucei and cytotoxicity against human embryonic kidney (HEK)293 and hepatoblastoma (HepG2) cells. Several compounds exhibited potent antiparasitic activity; however, with the exception of one compound (4), selectivity remained a challenge due to associated cytotoxicity. These findings reinforce the relevance of redox-active scaffolds as privileged structures in the development of trypanocidal agents and highlight the need for further optimization to improve therapeutic windows.