Structure-activity relationship of phosmidosine: importance of the 7,8-dihydro-8-oxoadenosine residue for antitumor activity.

Abstract

To study the structure-activity relationship of phosmidosine, a variety of phosmidosine derivatives 9a-g were synthesized by condensation of N-diisopropyl N'-(N-tritylprolyl)phosphorodiamidite 6 with appropriately protected nucleoside derivatives 7a-g. As the result, replacement of the 7,8-dihydro-8-oxoadenine base by adenine and 6-N-acetyladenine did not affect the antitumor activity. However, phosmidosine derivatives containing uracil, cytosine, and guanine in place of the 7,8-dihydro-8-oxoadenine base did not show significant activity. A plausible explanation for the selective expression of phosmidosine compared with that of phosmidosine analogs having other amino acids in place of proline is also discussed. These results suggest that phosmidosine serves as an inhibitor of prolyl adenosine 5'-phosphate (prolyl-AMP) to inhibit the peptide synthesis in cancer-related cells.

• Authors: Mitsuo Sekine, Kazuhisa Okada, Kohji Seio, Hideaki Kakeya, Hiroyuki Osada, Takuma Sasaki
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 12 Issue 19 Pg. 5193-201 (Oct 01 2004) ISSN: 0968-0896 [Print] England
• PMID: 15351402 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Deoxyadenosines
• Purine Nucleotides
• phosmidosine
• 2'-deoxy-7,8-dihydro-8-oxoadenosine

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Deoxyadenosines (chemistry, pharmacology)
• Humans
• Inhibitory Concentration 50
• Protein Biosynthesis (drug effects)
• Purine Nucleotides (chemical synthesis, pharmacology)
• Structure-Activity Relationship