Ferrocenyl-chloroquine

These complexes were tested for in vitro antimalarial activity showing that the coordination to the Au increases the potency of chloroquine. The ferrocenyl ligands... 

Blackie, M.A.L., Beagley, P., Chibale, K., Clarkson, C., Moss, J.R. and Smith, P.J. (2003) Synthesis and antimalarial activity in vitro of new heterobimetallic complexes Rh and Au derivatives of chloroquine and a series of ferrocenyl-4-amino-7-chloroquinolines. Journal of Organometallic Chemistry, 688(1-2), 144-152. 

Fig. 3 Organometallic complexes of known organic antiproliferation agents designed to overcome drug resistance a ferrocenyl-penicillin derivatives b ferrocenyl-cephalosporin derivatives c rhodium chloroquine complex d ferrocenjd-chloroquine derivative e iri-dium-COD-pentamidine complex...

The specific properties of ferroquine, certain of which encompass the structure-function relationship proposed for chloroquine [140] are the following. (1) Maintenance of a 4-aminoquinoline entity for vacuolar accumulation by pH trapping and haematin association (2) A side chain comprising a basic amino group, to provide strong antiplasmodial activity (3) A ferrocenyl group for its lipophilic (log Po/w=3.3) and redox (ferrocene/ferricinium Eg =+460 mV) properties (4) A rapid and cheap synthetic method, involving few steps. 

Recently, chloroquine has been successfully modified with a ferrocenyl entity incorporated widiin the side chain of the drug. This drug named ferroquine is active against chloroquine-resistant strains of die malaria parasite (38). This molecule is an example of the development of bioorganometallic chemistry in die design of drugs. 

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