Study on the synthesis and PKA-I binding activities of 5-alkynyl tubercidin analogues

Bioorg Med Chem. 2002 Apr;10(4):907-12. doi: 10.1016/s0968-0896(01)00341-8.

Abstract

5-alkynyl tubercidin analogues were synthesized and their biological activities were evaluated. It was found that protein kinase A could be activated by 5-alkynyl tubercidin (9a) and cAMP-binding ability to PKA-I was selectively inhibited by it. Molecular modeling showed that the interaction of 9a and PKA-I was associated with the existence of hydrophobic alkynyl group. During the synthesis of tubercidin analogues, a pair of 2'-carbonyl participating abnormal coupling products (11a, 11b) was obtained, the structure was identified by X-ray crystalline diffraction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Division / drug effects
  • Crystallography, X-Ray
  • Cyclic AMP / antagonists & inhibitors
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular
  • Molecular Structure
  • Protein Binding
  • Structure-Activity Relationship
  • Tubercidin / analogs & derivatives*
  • Tubercidin / chemical synthesis
  • Tubercidin / pharmacology
  • Tumor Cells, Cultured

Substances

  • Alkynes
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Tubercidin