Synthesis and biological activity of novel N6-substituted and 2,N6-disubstituted adenine ribo- and 3′-C-methyl- ribonucleosides as antitumor agents

Loredana Cappellacci, Riccardo Petrelli, Palmarisa Franchetti, Patrizia Vita, Praveen Kusumanchi, Mohineesh Kumar, Hiremagalur N. Jayaram, Bingsen Zhou, Yun Yen, Mario Grifantini

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16 Scopus citations

Abstract

A series of N6-aminopurine-9-β-d-ribonucleosides and ribose-modified 3′-C-methyl analogues substituted at N6- position with a small group like hydroxy, methoxy or amino group or at C2(N 6) position have been synthesized and tested against a panel of human leukemia and carcinoma cell lines. N6-Hydrazino-9-β-d- ribofuranosyl-purine (5) displayed the best antiproliferative activity in the low micromolar or submicromolar range against all tested tumor cell lines. The activity of this nucleoside is related in part to ribonucleotide reductase inhibition. C2-modification or 3′-C-methylation in N6- substituted adenosine analogues leads to a decrease or loss in activity.

Original languageEnglish (US)
Pages (from-to)1499-1504
Number of pages6
JournalEuropean Journal of Medicinal Chemistry
Volume46
Issue number5
DOIs
StatePublished - May 1 2011

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Keywords

  • 3′-C-Methyladenosine
  • Antitumor activity
  • Purine ribonucleosides
  • Ribonucleotide reductase inhibitors

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Cappellacci, L., Petrelli, R., Franchetti, P., Vita, P., Kusumanchi, P., Kumar, M., Jayaram, H. N., Zhou, B., Yen, Y., & Grifantini, M. (2011). Synthesis and biological activity of novel N6-substituted and 2,N6-disubstituted adenine ribo- and 3′-C-methyl- ribonucleosides as antitumor agents. European Journal of Medicinal Chemistry, 46(5), 1499-1504. https://doi.org/10.1016/j.ejmech.2011.01.055