Targeting Sensitive-Strain and Resistant-Strain Malaria Parasites Through a Metal-Based Approach

Millions of people are affected annually by infectious, parasitic diseases such as malaria. With the emergence of resistance to conventional chemotherapeutics, new strategies are needed to fast-track the synthesis of more efficient drugs and provide novel mechanisms of action to stem the tide of rising resistance. The derivatization of molecules of known biological significance with transition metals has emerged as one such potential strategy, exemplified by the discovery of the most prominent candidate thus far, ferroquine. Chapter 10 highlights work from our research group in which we have systematically introduced transition metals, particularly platinum group metals (PGMs) into organic compounds of known biological significance, to develop new antimalarial drug leads. We describe our strategies based on: (i) small molecule platforms; and (ii) multivalent / macromolecular platforms, aimed at targeting resistant strains. We also expound on possible mechanisms of actions of the most active potential drug leads