title: Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 1.
abstract: Potent and selective Candida albicans N-myristoyltransferase (CaNmt) inhibitors have been identified through optimization of a lead compound 1 discovered by random screening. The inhibitor design is based on the crystal structure of the CaNmt complex with compound (S)-3 and structure-activity relationships (SARs) have been clarified. Modification of the C-4 side chain of 1 has led to the discovery of a potent and selective CaNmt inhibitor 11 (RO-09-4609), which exhibits antifungal activity against C. albicans in vitro.
authors.affiliation: Nippon Roche Research Center, 200 Kajiwara, Kamakura, 247-8530, Kanagawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Masubuchi
authors.forename: K
authors.initials: K
authors.lastname: Kawasaki
authors.forename: H
authors.initials: H
authors.lastname: Ebiike
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: S
authors.initials: S
authors.lastname: Tsujii
authors.forename: S
authors.initials: S
authors.lastname: Sogabe
authors.forename: T
authors.initials: T
authors.lastname: Fujii
authors.forename: K
authors.initials: K
authors.lastname: Sakata
authors.forename: Y
authors.initials: Y
authors.lastname: Shiratori
authors.forename: Y
authors.initials: Y
authors.lastname: Aoki
authors.forename: T
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: N
authors.initials: N
authors.lastname: Shimma
mesh_terms: D000217:Acyltransferases / Q000187:drug effects*; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D001572:Benzofurans; D011943:Receptors, Adrenergic, beta; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase