Mono- and bis-thiazolium salts have potent antimalarial activity

Three new series comprising 24 novel cationic choline analogues and consisting of mono- or his (N or C-5-duplicated) thiazolium salts have been synthesized. Bis-thiazolium salts showed potent antimalarial activity (much superior to monothiazoliums). Among them, bis-thiazolium salts 12 and 13 exhibited IC50 values of 2.25 nM and 0.65 nM, respectively, against P. falciparum in vitro. These compounds also demonstrated good in vivo activity (ED50 <= 0.22 mg/kg), and low toxicity in mice infected by Plasmodium vinckei.