Design and Synthesis of Inhibitors of <i>Plasmodium falciparum N</i>-Myristoyltransferase, A Promising Target for Antimalarial Drug Discovery

Design of inhibitors for <i>N</i>-myristoyltransferase (NMT), an enzyme responsible for protein trafficking in Plasmodium falciparum, the most lethal species of parasites that cause malaria, is described. Chemistry-driven optimization of compound <b>1</b> from a focused NMT inhibitor library led to the identification of two early lead compounds <b>4</b> and <b>25</b>, which showed good enzyme and cellular potency and excellent selectivity over human NMT. These molecules provide a valuable starting point for further development