Seite - (000342) - in Biomedical Chemistry: Current Trends and Developments

target population. Pro-drugs activated by CYPs 3A4, 2D6, or 2C19 may lack efficacy in some populations due to high polymorphism. If at all possible, non-CYP mediated conversion is desirable to avoid such liabilities in later development. Likewise, toxicity can be affected in a similar manner if, for example, the formation of a reactive metabolite is mediated by a highly polymorphic CYP. Table 3.4.1: Approaches to antimalarial drug discovery and development. Adapted from Philip J. Rosenthal’s review on Antimalarial drug discovery: old and new approaches (Rosenthal, 2003). Approach Examples Optimize therapy with existing drugs (combinations) Amodiaquine/sulfadoxine/pyrimethamine Amodiaquine/artesunate Artesunate/sulfadoxine/pyrimethamine Artesunate/mefloquine Artemether/lumefantrine Chlorproguanil/dapsone Chlorproguanil/dapsone/artesunate Atovaquone/proguanil Develop analogs of existing drugs New aminoquinolines New endoperoxides New folate antagonists Natural Products New natural products Repurposing of drugs from other therapeutic areas Folate antagonists Antibiotics Atovaquone Iron chelators Reversing drug resistance Verapamil, desipramine, trifluoperazine, chlorpheniramine Discovery of compounds active against novel targets Antibiotics, Quinolones, etc.