Preparation, biological activity and endogenous occurrence of N6-benzyladenosines

Bioorg Med Chem. 2007 Jun 1;15(11):3737-47. doi: 10.1016/j.bmc.2007.03.038. Epub 2007 Mar 16.

Abstract

Cytokinin activity of forty-eight 6-benzyladenosine derivatives at both the receptor and cellular levels as well as their anticancer properties were compared in various in vitro assays. The compounds were prepared by the condensation of 6-chloropurine riboside with corresponding substituted benzylamines and characterized by standard collection of physico-chemical methods. The majority of synthesized derivatives exhibited high activity in all three of the cytokinin bioassays used (tobacco callus, wheat leaf senescence and Amaranthus bioassay). The highest activities were observed in the senescence bioassay. For several of the compounds tested, significant differences in activity were found between the bioassays used, indicating that diverse recognition systems may operate. This suggests that it may be possible to modulate particular cytokinin-dependent processes with specific compounds. In contrast to their high activity in bioassays, the tested compounds were recognized with only very low sensitivity in both Arabidopsis thaliana AHK3 and AHK4 receptor assays. The prepared derivatives were also investigated for their antiproliferative properties on cancer and normal cell lines. Several of them showed very strong cytotoxic activity against various cancer cell lines. On the other hand, they were not cytotoxic for normal murine fibroblast (NIH/3T3) cell line. This anticancer activity of cytokinin ribosides may be important, given that several of them occur as endogenous compounds in different organisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry
  • Adenosine / pharmacology
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Arabidopsis Proteins
  • Biological Assay
  • Cells, Cultured
  • Cytokinins / chemical synthesis
  • Cytokinins / chemistry*
  • Cytokinins / pharmacology*
  • Fibroblasts / drug effects
  • Histidine Kinase
  • Mice
  • NIH 3T3 Cells
  • Plant Cells
  • Plants / drug effects
  • Protein Kinases
  • Receptors, Cell Surface

Substances

  • Antineoplastic Agents
  • Arabidopsis Proteins
  • Cytokinins
  • Receptors, Cell Surface
  • N(6)-benzyladenosine
  • Protein Kinases
  • Histidine Kinase
  • AHK3 protein, Arabidopsis
  • WOL protein, Arabidopsis
  • Adenosine