Development of novel 1,4-benzodiazepine-based Michael acceptors as antitrypanosomal agents

Novel 1,4-benzodiazepines, endowed with a Michael acceptor moiety, were designed taking advantage of a computational prediction of their pharmacokinetic parameters. Among all the synthesized derivatives, we identified a new lead compound (i.e., 4a), bearing a vinyl ketone warhead and endowed with a promising antitrypanosomal activity against Trypanosoma brucei brucei (IC50 = 5.29 μM), coupled with a lack of cytotoxicity towards mammalian cells (TC50 >100 μM).

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide