title: Synthesis and anticancer activity of (RS)-9-(2,3-dihydro-1,4-benzoxaheteroin-2-ylmethyl)-9H-purines.
abstract: Herein are reported the synthesis and anticancer activity against the human breast cancer cell line MCF-7 of a series of substituted (RS)-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9H-purine derivatives and (RS)-9-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-9H-purine derivatives. When the Mitsunobu reaction was carried out between (RS)-2,3-dihydro-1,4-benzoxathiin-3-methanol and the heterocyclic bases 6-chloro-, 2,6-dichloro, and 6-bromo-purines under microwave-assisted conditions, a formal 1,4-sulfur migration takes place through two consecutive oxyranium and episulfonium rings, giving rise to the corresponding (RS)-9-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-9H-purine derivatives, previously reported by us. The most active compound (RS)-2,6-dichloro-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9H-purine shows an IC(50) = 2.75 ± 0.02 μM. When the cancerous cells were treated with this compound, a significant increase of apoptotic cells (70.08 ± 0.33%) was obtained in relation to the control ones. The induction of the G(2)/M cell cycle arrest and apoptosis by the three most active compounds is associated with increased phosphorylation of eIF2α in human breast cancer cells.
authors.affiliation: Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, 18071 Granada, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Conejo-García
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: García-Rubiño
authors.forename: Juan A
authors.initials: JA
authors.lastname: Marchal
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Núñez
authors.forename: Alberto
authors.initials: A
authors.lastname: Ramírez
authors.forename: Sandro
authors.initials: S
authors.lastname: Cimino
authors.forename: M Ángel
authors.initials: MÁ
authors.lastname: García
authors.forename: Antonia
authors.initials: A
authors.lastname: Aránega
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gallo
authors.forename: Joaquín M
authors.initials: JM
authors.lastname: Campos
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011687:Purines