1040031-35-3Relevant academic research and scientific papers
Design, synthesis and anti flaviviridae activity of N6-, 5′,3′-O- and 5′,2′-O-substituted adenine nucleoside analogs
Angusti, Angela,Manfredini, Stefano,Durini, Elisa,Ciliberti, Nunzia,Vertuani, Silvia,Solaroli, Nicola,Pricl, Sabrina,Ferrone, Marco,Fermeglia, Maurizio,Loddo, Roberta,Secci, Barbara,Visioli, Anna,Sanna, Tiziana,Collu, Gabriella,Pezzullo, Margherita,La Colla, Paolo
experimental part, p. 423 - 432 (2009/04/11)
During a random screening of representative libraries of nucleoside analogues we discovered that the adenine derivatives FEVB28 and FEG118 were Flaviviridae inhibitors endowed with potency comparable, if not superior, to that of ribavirin. Those studies prompted us to design a new class of protected nucleoside analogs, reported herein, which displays interesting anti-bovine viral diarrhea virus (BVDV) activity and low cytotoxicity in cell-based assays (4, 23, 29 EC50: 14, 11, 26 μM respectively, CC50 > 100 μM) and appreciable activity in enzyme assays against the RNA dependent RNA polymerase (RdRp) of BVDV (4, 23, 29, RdRp inhibition activity 27, 16, 15 μM respectively). A molecular modeling study was also carried out to highlight the possible interactions between this compounds class and the corresponding hepatitis C virus (HCV) enzyme.
Anticancer and antiviral effects and inactivation of S-adenosyl-L- homocysteine hydrolase with 5'-carboxaldehydes and oximes synthesized from adenosine and sugar-modified analogues
Wnuk, Stanislaw F.,Yuan, Chong-Sheng,Borchardt, Ronald T.,Balzarini, Jan,De Clercq, Erik,Robins, Morris J.
, p. 1608 - 1618 (2007/10/03)
Selectively protected adenine nucleosides were converted into 5'- carboxaldehyde analogues by Moffatt oxidation (dimethyl sulfoxide/dicyclohexylcarbodiimide/dichloroacetic acid) or with the Dess- Martin periodinane reagent. Hydrolysis of a 5'-fluoro-5'-S-methyl-5'-thio (α-fluoro thioether) arabinosyl derivative also gave the 5'-carboxaldehyde. Treatment of 5'-carboxaldehydes with hydroxylamine [or O-(methyl, ethyl, and benzyl)hydroxylamine] hydrochloride gave E/Z oximes. Treatment of purified oximes with aqueous trifluoroacetic acid and acetone effected trans-oximation to provide clean samples of 5'-carboxaldehydes. Adenosine (Ado)-5'- carboxaldehyde and its 4'-epimer are potent inhibitors of S-adenosyl-L- homocysteine (AdoHcy) hydrolase. They bind efficiently to the enzyme and undergo oxidation at C3' to give 3'-keto analogues with concomitant reduction of the NAD+ cofactor to give an inactive, tightly bound NADH-enzyme complex (type I cofactor-depletion inhibition). Potent type I inhibition was observed with 5'-carboxaldehydes that contain a ribo cis-2',3'-glycol. Their oxime derivatives are 'proinhibitors' that undergo enzyme-catalyzed hydrolysis to release the inhibitors at the active site. The 2'-deoxy and 2'-epimeric (arabinosyl) analogues were much weaker inhibitors, and the 3'-deoxy compounds bind very weakly. Ado-5'-carboxaldehyde oxime had potent cytotoxicity in tumor cell lines and was toxic to normal human cells. Analogues had weaker cytotoxic and antiviral potencies, and the 3'-deoxy compounds were essentially devoid of cytotoxic and antiviral activity.
