Ferroquine: A Concealed Weapon (original) (raw)

Molecular Approaches toward Targeted Drug Development, 2011

Abstract

ABSTRACT The development of ferroquine (FQ; SR97193) is the result of a successful strategy consisting of the incorporation of a ferrocene moiety into the structure of chloroquine (CQ) to overcome the resistance of Plasmodium falciparum to the parent drug, or to improve its antimalarial action. This approach has been applied to several classes of known antimalarials (arylaminoalcohols, artemisinin derivatives, naphthoquinones), without any real gain of activity. Nevertheless, the modification of amino-4-quinolines and, more recently, of fluoroquinolones has provided highly significant results. The efficacy of ferrocene-quinoline antimalarials is directly dependent not only on the position of ferrocene in the molecule, but also on several other properties of the drugs. Among numerous molecules synthesized, FQ appears so far to be the most promising among antimalarials currently in development. The potent activity of FQ and the absence of cross-resistance with other antimalarials were demonstrated both in vitro on a large number of clones and field isolates of P. falciparum, and in vivo on rodent models that demonstrated the high bioavailability of the product. Excellent properties of FQ were observed during a pharmacology survey. The drug has been developed by Sanofi-Aventis, and is currently in Phase IIb clinical trials.

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