Abstract
Inhibition of Plasmodium falciparum nicotinamidase could represent a potential antimalarial since parasites require nicotinic acid to successfully recycle nicotinamide to NAD+, and importantly, humans lack this biosynthetic enzyme. Recently, mechanism-based inhibitors of nicotinamidase have been discovered. The most potent compound inhibits both recombinant P. falciparum nicotinamidase and parasites replication in infected human red blood cells (RBCs). These studies provide evidence for the importance of nicotinamide salvage through nicotinamidase as a central master player of NAD+ homeostasis in P. falciparum.