Table of Contents
Metal-Based Drugs
Volume 2008 (2008), Article ID 495123, 10 pages
http://dx.doi.org/10.1155/2008/495123
Review Article

Metallocene Antimalarials: The Continuing Quest

1Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
2Institute of Infectious Disease and Molecular Medicine, UCT Faculty Of Health Sciences, University of Cape Town, Observatory 7925, South Africa

Received 20 June 2007; Accepted 23 August 2007

Academic Editor: Jannie C. Swarts

Copyright © 2008 Margaret A. L. Blackie and Kelly Chibale. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Over the last decade, a significant body of research has been developed around the inclusion of a metallocene moiety into known antimalarial compounds. Ferroquine is the most successful of these compounds. Herein, we describe our contribution to metallocene antimalarials. Our approach has sought to introduce diversity sites in the side chain of ferroquine in order to develop a series of ferroquine derivatives. The replacement of the ferrocenyl moiety with ruthenocene has given rise to ruthenoquine and a modest series of analogues. The reaction of ferroquine and selected analogues with Au(PPh3)NO3, Au(C6F5)(tht), and [Rh(COD)Cl2] has resulted in a series of heterobimetallic derivatives. In all cases, compounds have been evaluated for in vitro antiplasmodial activity in both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Preliminary structure-activity relationships have been delineated.