Synthesis of Ferroquine Enantiomers: First Investigation of Effects of Metallocenic Chirality upon Antimalarial Activity and Cytotoxicity

Abstract

Ferroquine (FQ) is a new antimalarial agent with a high blood schizotoncidal activity. Previous studies on this compound were done with racemate mixtures. As FQ possesses planar chirality, pure enantiomers were obtained by enzymatic resolution in order to compare their antimalarial activities and cytotoxicities. (+)-FQ and (-)-FQ were equally active in vitro, at nanomolar concentrations. Both enantiomers were slightly less active than the racemate in vivo; cytotoxicities were similar. Actually, the racemate represents the optimal formulation. To the best of our knowledge, this is the first investigation of biological activities of compounds with metallocenic chirality.