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

doi:10.1016/j.ejmech.2011.01.055

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

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

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 language	English
Pages (from-to)	1499-1504
Number of pages	6
Journal	European Journal of Medicinal Chemistry
Volume	46
Issue number	5
DOIs	https://doi.org/10.1016/j.ejmech.2011.01.055
Publication status	Published - May 2011
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

Access to Document

10.1016/j.ejmech.2011.01.055

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

Synthesis and biological activity of novel N⁶-substituted and 2,N⁶-disubstituted adenine ribo- and 3′-C-methyl- ribonucleosides as antitumor agents. / Cappellacci, Loredana; Petrelli, Riccardo; Franchetti, Palmarisa et al.

In: European Journal of Medicinal Chemistry, Vol. 46, No. 5, 05.2011, p. 1499-1504.

Research output: Contribution to journal › Article › peer-review

Cappellacci, L, Petrelli, R, Franchetti, P, Vita, P, Kusumanchi, P, Kumar, M, Jayaram, HN, 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, vol. 46, no. 5, pp. 1499-1504. https://doi.org/10.1016/j.ejmech.2011.01.055

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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.",

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