Carbocyclic adenosine analogues as S-adenosylhomocysteine hydrolase inhibitors and antiviral agents: recent advances.
Various carbocyclic analogues of adenosine, including aristeromycin (carbocyclic adenosine), carbocyclic 3-deazaadenosine, neplanocin A, 3-deazaneplanocin A, the 5'-nor derivatives of aristeromycin, carbocylic 3-deazaadenosine, neplanocin A and 3-deazaneplanocin A, and the 2-halo (i.e., 2-fluoro) and 6'-R-alkyl (i.e., 6'-R-methyl) derivatives of neplanocin A have been recognized as potent inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase. This enzyme plays a key role in methylation reactions depending on S-adenosylmethionine (AdoMet) as methyl donor. AdoHcy hydrolase inhibitors have been shown to exert broad-spectrum antiviral activity against pox-, paramyxo-, rhabdo-, filo-, bunya-, arena-, and reoviruses. They also interfere with the replication of human immunodeficiency virus through inhibition of the Tat transactivation process.
De Clercq
E
E
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium. Erik.DeClercq@rega.kuleuven.ac.be
D000241:Adenosine / Q000031:analogs & derivatives*; D043383:Adenosylhomocysteinase; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection / Q000235:genetics
D000903:Antibiotics, Antineoplastic; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000241:Adenosine