title: Design, synthesis, and biological evaluation of fluoroneplanocin A as the novel mechanism-based inhibitor of S-adenosylhomocysteine hydrolase.
abstract: Fluoroneplanocin A (12) was designed as a novel mechanism-based inhibitor of S-adenosylhomocysteine hydrolase (SAH) and efficiently synthesized via an electrophilic vinyl fluorination reaction (n-BuLi, N-fluorobenzenesulfonimide at -78 degrees C). Fluoroneplanocin A exhibited 2-fold more potent SAH inhibitory activity than the parent neplanocin A. A new mechanism of irreversible inhibition discovered in this work might provide new alternatives in the design of a different class of antiviral agents operating via SAH inhibition.
authors.affiliation: Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea. lakjeong@ewha.ac.kr
authors.forename: Lak Shin
authors.initials: LS
authors.lastname: Jeong
authors.forename: Su Jeong
authors.initials: SJ
authors.lastname: Yoo
authors.forename: Kang Man
authors.initials: KM
authors.lastname: Lee
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Koo
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Choi
authors.forename: Hea Ok
authors.initials: HO
authors.lastname: Kim
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Jae Gyu
authors.initials: JG
authors.lastname: Park
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
authors.forename: Moon Woo
authors.initials: MW
authors.lastname: Chun
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D043383:Adenosylhomocysteinase; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; C470754:fluoroneplanocin A; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000241:Adenosine