title: Synthesis and biological activity of novel N6-substituted and 2,N6-disubstituted adenine ribo- and 3'-C-methyl-ribonucleosides as antitumor agents.
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(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.
authors.affiliation: School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, 62032 Camerino, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Cappellacci
authors.forename: Riccardo
authors.initials: R
authors.lastname: Petrelli
authors.forename: Palmarisa
authors.initials: P
authors.lastname: Franchetti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vita
authors.forename: Praveen
authors.initials: P
authors.lastname: Kusumanchi
authors.forename: Mohineesh
authors.initials: M
authors.lastname: Kumar
authors.forename: Hiremagalur N
authors.initials: HN
authors.lastname: Jayaram
authors.forename: Bingsen
authors.initials: B
authors.lastname: Zhou
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
authors.forename: Mario
authors.initials: M
authors.lastname: Grifantini
mesh_terms: D000225:Adenine / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000378:metabolism; D012263:Ribonucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012264:Ribonucleotide Reductases / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D012263:Ribonucleosides; D012264:Ribonucleotide Reductases; D000225:Adenine