title: New antitumor 6-chloropurine nucleosides inducing apoptosis and G2/M cell cycle arrest.
abstract: Treating cancer has been challenging for decades, following countless approaches and attempts. Nucleosides, alone or as part of nucleotides, are vital elements of living systems and have shown pharmacological effects, e.g. as antibiotic or antiviral agents. We investigated the antitumor potential on human melanoma, lung and ovarian carcinomas, and on colon adenocarcinoma of a new series of purine nucleosides based on a 6-chloropurine or a 2-acetamido-6-chloropurine scaffold linked to perbenzylated hexosyl (glucosyl, galactosyl and mannosyl) residues. All compounds were tested in a sulforhodamine B (SRB) assay for their cytotoxicity and provided micromolar GI50 values with order of magnitude comparable to structurally similar chemotherapeutics, namely 2-chloro-2'-deoxyadenosine (cladribine). Furthermore, the induction of apoptosis was established and cell cycle analysis was accomplished demonstrating a G2/M cell cycle arrest.
authors.affiliation: Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, Ed. C8, Piso 5, 1749-016 Lisboa, Portugal; Bereich Organische Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwarz
authors.affiliation: Bereich Organische Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
authors.forename: Bianka
authors.initials: B
authors.lastname: Siewert
authors.affiliation: Bereich Organische Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
authors.forename: René
authors.initials: R
authors.lastname: Csuk
authors.affiliation: Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, Ed. C8, Piso 5, 1749-016 Lisboa, Portugal. Electronic address: aprauter@fc.ul.pt.
authors.forename: Amélia P
authors.initials: AP
authors.lastname: Rauter
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D019073:HT29 Cells; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D011684:Purine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006846:Hydrocarbons, Halogenated; D011684:Purine Nucleosides
keywords: 6-Chloropurine; Acridine orange; Antitumor; Cell cycle analysis; N-glycosylation; SRB assay