**11.3 Covalent bitherapy**

Covalent bitherapy entails the covalent bonding of two chemical moieties that act on different/same biological targets through different mechanisms of action [103–105]. Trioxaquine (SAR116242) is a synthetic hybrid compound with 1,2,4 trioxane and 4-aminoquinoline pharmacophores covalently related [106–108]. Since covalently linked pharmacophore is designed to target the parasite by: alkylation of heme with the trioxane moiety and binding of heme with the aminoquinoline moiety to inhibit hemozoin formation [109, 110], trioxaquine has been found to work on both asexual and sexual stages of malaria parasites.
