266349-27-3Relevant academic research and scientific papers
Doubly homologated dihalovinyl and acetylene analogues of adenosine: Synthesis, interaction with S-adenosyl-L-homocysteine hydrolase, and antiviral and cytostatic effects
Wnuk, Stanislaw F.,Valdez, Carlos A.,Khan, Jahanzeb,Moutinho, Priscilla,Robins, Morris J.,Yang, Xiaoda,Borchardt, Ronald T.,Balzarini, Jan,De Clercq, Erik
, p. 1180 - 1186 (2007/10/03)
Treatment of the 6-aldehyde derived by Moffatt oxidation of 3-O-benzoyl- 1,2-O-isopropylideneα-D-ribo-hexofuranose (2c) with the dibromo- or bromofluoromethylene Wittig reagents generated in situ with tetrabromomethane or tribromofluoromethane, triphenylphosphine, and zinc gave the dihalomethyleneheptofuranose analogues 3b and 3d, respectively. Acetolysis, coupling with adenine, and deprotection gave 9-(7,7-dibromo-5,6,7-trideoxy- β-D-ribo-hept-6-enofuranosyl)adenine (5a) or its bromofluoro analogue 5b. Treatment of 5a with excess butyllithium provided the acetylenic derivative 9-(5,6,7-trideoxy-β-D-ribo-hept-6-ynofuranosyl)adenine (6). The doubly homologated vinyl halides 5a and 5b and acetylenic 6 adenine nucleosides were designed as putative substrates of the 'hydrolytic activity' of S-adenosyl-L- homocysteine (AdoHcy) hydrolase. Incubation of AdoHcy hydrolase with 5a, 5b, and 6 resulted in time- and concentration-dependent inactivation of the enzyme (K(i): 8.5 ± 0.5, 17 ± 2, and 8.6 ± 0.5 μM, respectively), as well as partial reduction of enzyme-bound NAD+ to E-NADH. However, no products of the 'hydrolytic activity' were observed indicating these compounds are type I mechanism-based inhibitors. The compounds displayed minimal antiviral and cytostatic activity, except for 6, against vaccinia virus and vesicular stomatitis virus (IC50: 15 and 7 μM, respectively). These viruses typically fall within the activity spectrum of AdoHcy hydrolase inhibitors.
