Antitumor activity of C-methyl-β-D-ribofuranosyladenine nucleoside ribonucleotide reductase inhibitors

Palmarisa Franchetti, Loredana Cappellacci, Michela Pasqualini, Riccardo Petrelli, Patrizia Vita, Hiremagalur N. Jayaram, Zsuzsanna Horvath, Thomas Szekeres, Mario Grifantini

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

A series of adenosine derivatives substituted at the 1′-, 2′-, or 3′-position of the ribose ring with a methyl group was synthesized and evaluated for antitumor activity. From this study 3′-C-methyladenosine (3′-Me-Ado) emerged as the most active compound, showing activity against human myelogenous leukemia K562, multidrug resistant human leukemia K562IU, human promyelocytic leukemia HL-60, human colon carcinoma HT-29, and human breast carcinoma MCF-7 cell lines with IC50 values ranging from 11 to 38 μM. Structure-activity relationship studies showed that the structure of 3′-Me-Ado is crucial for the activity. Substitution of a hydrogen atom of the N6-amino group with a small alkyl or cycloalkyl group, the introduction of a chlorine atom in the 2-position of the purine ring, or the moving of the methyl group from the 3′-position to other ribose positions brought about a decrease or loss of antitumor activity. The antiproliferative activity of 3′-Me-Ado appears to be related to its ability to deplete both intracellular purine and pyrimidine deoxynucleotides through ribonucleotide reductase inhibition.

Original languageEnglish
Pages (from-to)4983-4989
Number of pages7
JournalJournal of Medicinal Chemistry
Volume48
Issue number15
DOIs
StatePublished - Jul 28 2005

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Ribonucleotide Reductases
Nucleosides
Ribose
Atoms
Leukemia
Chlorine
Adenosine
Myeloid Leukemia
Hydrogen
MCF-7 Cells
Substitution reactions
Structure-Activity Relationship
Cells
Human Activities
Inhibitory Concentration 50
Derivatives
Colon
Breast Neoplasms
Carcinoma
Cell Line

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Franchetti, P., Cappellacci, L., Pasqualini, M., Petrelli, R., Vita, P., Jayaram, H. N., ... Grifantini, M. (2005). Antitumor activity of C-methyl-β-D-ribofuranosyladenine nucleoside ribonucleotide reductase inhibitors. Journal of Medicinal Chemistry, 48(15), 4983-4989. https://doi.org/10.1021/jm048944c

Antitumor activity of C-methyl-β-D-ribofuranosyladenine nucleoside ribonucleotide reductase inhibitors. / Franchetti, Palmarisa; Cappellacci, Loredana; Pasqualini, Michela; Petrelli, Riccardo; Vita, Patrizia; Jayaram, Hiremagalur N.; Horvath, Zsuzsanna; Szekeres, Thomas; Grifantini, Mario.

In: Journal of Medicinal Chemistry, Vol. 48, No. 15, 28.07.2005, p. 4983-4989.

Research output: Contribution to journalArticle

Franchetti, P, Cappellacci, L, Pasqualini, M, Petrelli, R, Vita, P, Jayaram, HN, Horvath, Z, Szekeres, T & Grifantini, M 2005, 'Antitumor activity of C-methyl-β-D-ribofuranosyladenine nucleoside ribonucleotide reductase inhibitors', Journal of Medicinal Chemistry, vol. 48, no. 15, pp. 4983-4989. https://doi.org/10.1021/jm048944c
Franchetti P, Cappellacci L, Pasqualini M, Petrelli R, Vita P, Jayaram HN et al. Antitumor activity of C-methyl-β-D-ribofuranosyladenine nucleoside ribonucleotide reductase inhibitors. Journal of Medicinal Chemistry. 2005 Jul 28;48(15):4983-4989. https://doi.org/10.1021/jm048944c
Franchetti, Palmarisa ; Cappellacci, Loredana ; Pasqualini, Michela ; Petrelli, Riccardo ; Vita, Patrizia ; Jayaram, Hiremagalur N. ; Horvath, Zsuzsanna ; Szekeres, Thomas ; Grifantini, Mario. / Antitumor activity of C-methyl-β-D-ribofuranosyladenine nucleoside ribonucleotide reductase inhibitors. In: Journal of Medicinal Chemistry. 2005 ; Vol. 48, No. 15. pp. 4983-4989.
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