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

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• 作者：Loredana Cappellacci ; Riccardo Petrelli ; Palmarisa Franchetti ; Patrizia Vita ; Praveen Kusumanchi ; Mohineesh Kumar ; Hiremagalur N. Jayaram ; Bingsen Zhou ; Yun Yen ; Mario Grifantini
• 关键词：Purine ribonucleosides ; 3′ ; -C-Methyladenosine ; Antitumor activity ; Ribonucleotide reductase inhibitors
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：May 2011
• 年：2011
• 卷：46
• 期：5
• 页码：1499-1504
• 全文大小：270 K

文摘

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(N⁶) 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.