title: Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 3.
abstract: A new series of acid-stable antifungal agents having strong inhibitory activity against Candida albicans N-myristoyltransferase (CaNmt) has been developed starting from acid-unstable benzofuranylmethyl aryl ether 2. The inhibitor design is based on X-ray crystallographic analysis of a CaNmt complex with aryl ether 3. Among the new inhibitors, pyridine derivative 8b and benzimidazole derivative 8k showed clear antifungal activity in a murine systemic candidiasis model.
authors.affiliation: Department of Chemistry, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Miyako
authors.initials: M
authors.lastname: Masubuchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Morikami
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sogabe
authors.forename: Tsunehisa
authors.initials: T
authors.lastname: Aoyama
authors.forename: Hirosato
authors.initials: H
authors.lastname: Ebiike
authors.forename: Satoshi
authors.initials: S
authors.lastname: Niizuma
authors.forename: Michiko
authors.initials: M
authors.lastname: Hayase
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fujii
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Sakata
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Shindoh
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Shiratori
authors.forename: Yuko
authors.initials: Y
authors.lastname: Aoki
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shimma
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology; D004195:Disease Models, Animal; D015195:Drug Design; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D051379:Mice; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D001572:Benzofurans; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase