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Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

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ABSTRACT

A series of seventeen β-hydroxyphosphonate ribonucleoside analogues containing 4-substituted-1,2,3-triazoles was synthesized and fully characterized. Such compounds were designed as potential inhibitors of the cytosolic 5’-nucleotidase II (cN-II), an enzyme involved in the regulation of purine nucleotide pools. NMR and molecular modelling studies showed that a few derivatives adopted similar structural features to IMP or GMP. Five derivatives were identified as modest inhibitors with 53 to 64% of cN-II inhibition at 1 mM.

No MeSH data available.


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Superimposition of the docking poses obtained for IMP (pink sticks), derivatives 1n (cyan sticks) and 1q (green sticks) in the substrate binding site.
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Figure 7: Superimposition of the docking poses obtained for IMP (pink sticks), derivatives 1n (cyan sticks) and 1q (green sticks) in the substrate binding site.

Mentions: As the carbonyl group in position 6 of IMP is interacting with Arg202 in the crystal structure (distance of 3.0 Å in the crystal structure and 3.7 Å with derivative 1n), we expected that this functionality would constitute a good mimic of the hypoxanthine nucleobase (for IMP) as shown below (Fig. 7) with the superimposition of IMP (pink sticks) and derivatives 1n (cyan sticks) and 1q (green sticks) in the substrate binding site of cN-II.


Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation
Superimposition of the docking poses obtained for IMP (pink sticks), derivatives 1n (cyan sticks) and 1q (green sticks) in the substrate binding site.
© Copyright Policy - Beilstein
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4979751&req=5

Figure 7: Superimposition of the docking poses obtained for IMP (pink sticks), derivatives 1n (cyan sticks) and 1q (green sticks) in the substrate binding site.
Mentions: As the carbonyl group in position 6 of IMP is interacting with Arg202 in the crystal structure (distance of 3.0 Å in the crystal structure and 3.7 Å with derivative 1n), we expected that this functionality would constitute a good mimic of the hypoxanthine nucleobase (for IMP) as shown below (Fig. 7) with the superimposition of IMP (pink sticks) and derivatives 1n (cyan sticks) and 1q (green sticks) in the substrate binding site of cN-II.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

A series of seventeen β-hydroxyphosphonate ribonucleoside analogues containing 4-substituted-1,2,3-triazoles was synthesized and fully characterized. Such compounds were designed as potential inhibitors of the cytosolic 5’-nucleotidase II (cN-II), an enzyme involved in the regulation of purine nucleotide pools. NMR and molecular modelling studies showed that a few derivatives adopted similar structural features to IMP or GMP. Five derivatives were identified as modest inhibitors with 53 to 64% of cN-II inhibition at 1 mM.

No MeSH data available.


Related in: MedlinePlus