1. Design, synthesis, and biological evaluation of fluoroneplanocin A as the novel mechanism-based inhibitor of S-adenosylhomocysteine hydrolase.
- Author
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Jeong LS, Yoo SJ, Lee KM, Koo MJ, Choi WJ, Kim HO, Moon HR, Lee MY, Park JG, Lee SK, and Chun MW
- Subjects
- Adenosine analogs & derivatives, Adenosine chemistry, Adenosine pharmacology, Adenosylhomocysteinase, Animals, Antiviral Agents chemistry, Antiviral Agents pharmacology, Cell Line, Drug Design, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, HIV-1 drug effects, Herpesvirus 1, Human drug effects, Herpesvirus 2, Human drug effects, Humans, Vesicular stomatitis Indiana virus drug effects, Adenosine chemical synthesis, Antiviral Agents chemical synthesis, Enzyme Inhibitors chemical synthesis, Hydrolases antagonists & inhibitors
- 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.
- Published
- 2003
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