Design, synthesis, and biological evaluation of fluoroneplanocin A as the novel mechanism-based inhibitor of S-adenosylhomocysteine hydrolase.
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.
Jeong
Lak Shin
LS
Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea. lakjeong@ewha.ac.kr
Yoo
Su Jeong
SJ
Lee
Kang Man
KM
Koo
Mi Jeong
MJ
Choi
Won Jun
WJ
Kim
Hea Ok
HO
Moon
Hyung Ryong
HR
Lee
Min Young
MY
Park
Jae Gyu
JG
Lee
Sang Kook
SK
Chun
Moon Woo
MW
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
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; C470754:fluoroneplanocin A; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000241:Adenosine