Antileishmanial activity of quinazoline derivatives: Synthesis, docking screens, molecular dynamic simulations and electrochemical studies

•A quinazoline derivative (H2) as antileishmanial agent with low cytotoxicity was found.•H2 is active against promastigote and amastigote form of Leishmania mexicana.•H2 begins its antiparasitic action in less than 1 h, probably by oxidative mechanism.•H2 probably has a dual mechanism: oxidative stress inductor and DHFR inhibitors.

A series of quinazoline-2,4,6-triamine were synthesized and evaluated in vitro against Leishmania mexicana. Among them, N6-(ferrocenmethyl)quinazolin-2,4,6-triamine (H2) showed activity on promastigotes and intracellular amastigotes, as well as low cytotoxicity in mammalian cells. Docking and electrochemical studies showed the importance of both the ferrocene and the heterocyclic nucleus to the observed activity. H2 is readily oxidized electrochemically, indicating that the mechanism of action probably involves redox reactions.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide