Synthesis of New 5'-Norcarbocyclic Aza/Deaza Purine Fleximers - Noncompetitive Inhibitors of E.coli Purine Nucleoside Phosphorylase
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Khandazhinskaya, Anastasia, Ilja Fateev, Irina Konstantinova, Roman Esipov, Konstantin Polyakov, Katherine Seley-Radtke, Sergey Kochetkov, and Elena Matyugina. “Synthesis of New 5?-Norcarbocyclic Aza/Deaza Purine Fleximers - Noncompetitive Inhibitors of E.Coli Purine Nucleoside Phosphorylase.” Frontiers in Chemistry 10 (2022). https://www.frontiersin.org/articles/10.3389/fchem.2022.867587.
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Creative Commons Attribution 4.0 International (CC BY 4.0)
Creative Commons Attribution 4.0 International (CC BY 4.0)
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Abstract
A new series of flexible 5'-norcarbocyclic aza/deaza-purine nucleoside analogs were synthesized from 6-oxybicyclo[3.1.0.]hex-2-ene and pyrazole-containing fleximer analogs of heterocyclic bases using the Trost procedure. The compounds were evaluated as potential inhibitors of E. coli purine nucleoside phosphorylase. Analog 1-3 were found to be noncompetitive inhibitors with inhibition constants of 14–24 mM. From the data obtained, it can be assumed that the new 5'-norcarbocyclic nucleoside analogs interact with the active site of the PNP like natural heterocyclic bases. But at the same time the presence of a cyclopentyl moiety with 2' and 3' hydroxyls is necessary for the inhibitory properties, since compounds 8–10, without those groups did not exhibit an inhibitory effect under the experimental conditions.