Design, Synthesis, and Biological Evaluation of Fluoroneplanocin A as the Novel Mechanism-Based Inhibitor of S-Adenosylhomocysteine Hydrolase

• Published in: Journal of medicinal chemistry Vol. 46; no. 2; pp. 201 - 203
• Main Authors: Jeong, Lak Shin, Yoo, Su Jeong, Lee, Kang Man, Koo, Mi Jeong, Choi, Won Jun, Kim, Hea Ok, Moon, Hyung Ryong, Lee, Min Young, Park, Jae Gyu, Lee, Sang Kook, Chun, Moon Woo
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 16.01.2003; Amer Chemical Soc
• Subjects: Adenosine - analogs & derivatives; Adenosine - chemical synthesis; Adenosine - chemistry; Adenosine - pharmacology; Adenosylhomocysteinase; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Biological and medical sciences; Cell Line; Chemistry, Medicinal; Drug Design; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Herpesvirus 1, Human - drug effects; Herpesvirus 2, Human - drug effects; HIV-1 - drug effects; Humans; Hydrolases - antagonists & inhibitors; Life Sciences & Biomedicine; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Vesicular stomatitis Indiana virus - drug effects; INACTIVATION; HYDROLYTIC ACTIVITY; L-HOMOCYSTEINE HYDROLASE; ANALOGS; NUCLEOSIDES; ADENOSINE; ANTIVIRAL ACTIVITY; DERIVATIVES; Purine nucleoside; HIV-1 virus; Alphaherpesvirinae; Thioether hydrolases; Vesicular stomatitis virus; Irreversible reaction; Cyclitol; Rhabdoviridae; Adenosylhomocysteinase; Antiviral; Herpesvirus hominis; Chemical synthesis; Adenine derivatives; Haloalcohol; Enzyme; Herpesviridae; Retroviridae; Enzyme inhibitor; Lentivirus; In vitro; Biological activity; Virus; Mononegavirales; Vesiculovirus; Hydrolases; Fluorine Organic compounds; Human immunodeficiency virus; Ethylenic compound
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm025557z

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 °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.