The current state of antimalarial drug resistance emphasizes the need for new therapies with novel modes of action that will add a significant benefit compared with current standards. In this regard, high throughput phenotypic whole-cell screening aids the discovery of novel antiplasmodial scaffolds that are inherently suited to hit-to-lead and lead-optimization efforts. The aminothiazoles and aminopyridines exemplify two such compound classes stemming from whole-cell screening. Respective structure–activity relationship determinations and subsequent optimization around these scaffolds led to frontrunner compounds in each series, which possess the desired antimalarial efficacy, bioavailability and metabolic stability to further progress medicinal chemistry programs.
Paquet, T.; Gordon, R.; Waterson, D.; Witty, M.J.; Chibale, K. Antimalarial aminothiazoles and aminopyridines from phenotypic whole-cell screening of a SoftFocus®library. Future Medicinal Chemistry (2012) 4 (18) 2265-2277. [DOI: 10.4155/fmc.12.176]