A CoMSIA study on the adenosine kinase inhibition of pyrrolo[2,3-d]pyrimidine nucleoside analogues

Julio Caballero, Michael Fernández, Fernando D. González-Nilo

Resultado de la investigación: Article

5 Citas (Scopus)

Resumen

The structural requirements of pyrrolo[2,3-d]pyrimidine nucleoside (PPN) analogues as adenosine kinase (AK) inhibitors were in silico studied by using CoMSIA method. All models were trained with 32 compounds, after which they were evaluated for predictive ability with additional 5 compounds. Quantitative information on structure-activity trends is provided for further rational development and direction of selective synthesis. The best CoMSIA model included hydrophobic, H-bond donor and H-bond acceptor fields and had a good predictive quality according to internal validation criteria. In addition, this model predicted adequately the compounds contained in the test set. The analysis of the model gives a comprehensive qualitative and quantitative description of the molecular features at C4 and C5 positions of the pyrrolo[2,3-d]pyrimidine scaffold and C5-position of the β-d-ribofuranose of PPN analogues, relevant for a high AK inhibitory activity.

Idioma originalEnglish
Páginas (desde-hasta)5103-5108
Número de páginas6
PublicaciónBioorganic and Medicinal Chemistry
Volumen16
N.º9
DOI
EstadoPublished - 1 may 2008

Huella dactilar

Adenosine Kinase
Pyrimidine Nucleosides
Computer Simulation
Scaffolds

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Citar esto

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abstract = "The structural requirements of pyrrolo[2,3-d]pyrimidine nucleoside (PPN) analogues as adenosine kinase (AK) inhibitors were in silico studied by using CoMSIA method. All models were trained with 32 compounds, after which they were evaluated for predictive ability with additional 5 compounds. Quantitative information on structure-activity trends is provided for further rational development and direction of selective synthesis. The best CoMSIA model included hydrophobic, H-bond donor and H-bond acceptor fields and had a good predictive quality according to internal validation criteria. In addition, this model predicted adequately the compounds contained in the test set. The analysis of the model gives a comprehensive qualitative and quantitative description of the molecular features at C4 and C5 positions of the pyrrolo[2,3-d]pyrimidine scaffold and C5-position of the β-d-ribofuranose of PPN analogues, relevant for a high AK inhibitory activity.",
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A CoMSIA study on the adenosine kinase inhibition of pyrrolo[2,3-d]pyrimidine nucleoside analogues. / Caballero, Julio; Fernández, Michael; González-Nilo, Fernando D.

En: Bioorganic and Medicinal Chemistry, Vol. 16, N.º 9, 01.05.2008, p. 5103-5108.

Resultado de la investigación: Article

TY - JOUR

T1 - A CoMSIA study on the adenosine kinase inhibition of pyrrolo[2,3-d]pyrimidine nucleoside analogues

AU - Caballero, Julio

AU - Fernández, Michael

AU - González-Nilo, Fernando D.

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Y1 - 2008/5/1

N2 - The structural requirements of pyrrolo[2,3-d]pyrimidine nucleoside (PPN) analogues as adenosine kinase (AK) inhibitors were in silico studied by using CoMSIA method. All models were trained with 32 compounds, after which they were evaluated for predictive ability with additional 5 compounds. Quantitative information on structure-activity trends is provided for further rational development and direction of selective synthesis. The best CoMSIA model included hydrophobic, H-bond donor and H-bond acceptor fields and had a good predictive quality according to internal validation criteria. In addition, this model predicted adequately the compounds contained in the test set. The analysis of the model gives a comprehensive qualitative and quantitative description of the molecular features at C4 and C5 positions of the pyrrolo[2,3-d]pyrimidine scaffold and C5-position of the β-d-ribofuranose of PPN analogues, relevant for a high AK inhibitory activity.

AB - The structural requirements of pyrrolo[2,3-d]pyrimidine nucleoside (PPN) analogues as adenosine kinase (AK) inhibitors were in silico studied by using CoMSIA method. All models were trained with 32 compounds, after which they were evaluated for predictive ability with additional 5 compounds. Quantitative information on structure-activity trends is provided for further rational development and direction of selective synthesis. The best CoMSIA model included hydrophobic, H-bond donor and H-bond acceptor fields and had a good predictive quality according to internal validation criteria. In addition, this model predicted adequately the compounds contained in the test set. The analysis of the model gives a comprehensive qualitative and quantitative description of the molecular features at C4 and C5 positions of the pyrrolo[2,3-d]pyrimidine scaffold and C5-position of the β-d-ribofuranose of PPN analogues, relevant for a high AK inhibitory activity.

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KW - CoMSIA

KW - In silico drug design

KW - Quantitative structure-activity relationships

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