title: Synthesis and pharmacophore modelling of 2,6,9-trisubstituted purine derivatives and their potential role as apoptosis-inducing agents in cancer cell lines.
abstract: A series of 2,6,9-trisubstituted purine derivatives have been synthesized and investigated for their potential role as antitumor agents. Twelve compounds were obtained by a three step synthetic procedure using microwave irradiation in a pivotal step. All compounds were evaluated in vitro to determine their potential effect on cell toxicity by the MTT method and flow cytometry analysis on four cancer cells lines and Vero cells. Three out of twelve compounds were found to be promising agents compared to a known and effective anticancer drug, etoposide, in three out of four cancer cell lines assayed with considerable selectivity. Preliminary flow cytometry data suggests that compounds mentioned above induce apoptosis on these cells. The main structural requirements for their activity for each cancer cell line were characterized with a preliminary pharmacophore model, which identified aromatic centers, hydrogen acceptor/donor center and a hydrophobic area. These features were consistent with the cytotoxic activity of the assayed compounds.
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile. jeannettecalderon.a@gmail.com.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Calderón-Arancibia
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile. ccespino@uc.cl.
authors.forename: Christian
authors.initials: C
authors.lastname: Espinosa-Bustos
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile. acanetem@uc.cl.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Cañete-Molina
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile. rtapia@uc.cl.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Tapia
authors.affiliation: Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile. mfaundeza@uc.cl.
authors.forename: Mario
authors.initials: M
authors.lastname: Faúndez
authors.affiliation: Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile. mjtorres@uc.cl.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Torres
authors.affiliation: Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile. aaguirred@uc.cl.
authors.forename: Adam
authors.initials: A
authors.lastname: Aguirre
authors.affiliation: Centro de Bioinformática Estructural-DETEMA, Facultad de Química, Universidad de la República, C.C. 1157 Montevideo, Uruguay. margot.paulino@gmail.com.
authors.forename: Margot
authors.initials: M
authors.lastname: Paulino
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile. cosalas@uc.cl.
authors.forename: Cristian O
authors.initials: CO
authors.lastname: Salas
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011687:Purines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000970:Antineoplastic Agents; D011687:Purines