title: Design and synthesis of inhibitors of Plasmodium falciparum N-myristoyltransferase, a promising target for antimalarial drug discovery.
abstract: Design of inhibitors for N-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 1 from a focused NMT inhibitor library led to the identification of two early lead compounds 4 and 25, which showed good enzyme and cellular potency and excellent selectivity over human NMT. These molecules provide a valuable starting point for further development.
authors.affiliation: Department of Chemistry, Imperial College London, London SW7 2AZ, UK.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yu
authors.forename: James A
authors.initials: JA
authors.lastname: Brannigan
authors.forename: David K
authors.initials: DK
authors.lastname: Moss
authors.forename: A Marek
authors.initials: AM
authors.lastname: Brzozowski
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Wilkinson
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Holder
authors.forename: Edward W
authors.initials: EW
authors.lastname: Tate
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Leatherbarrow
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology*; D011487:Protein Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D001572:Benzofurans; D010880:Piperidines; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase