Synthesis and Pharmacophore Modelling of 2,6,9-Trisubstituted Purine Derivatives and Their Potential Role as Apoptosis-Inducing Agents in Cancer Cell Lines

Molecules

Jeannette Calderón-Arancibia⁴  Christian Espinosa-Bustos⁴  Álvaro Ca༞te-Molina⁴  Ricardo A. Tapia⁴  Mario Faúndez²  Maria Jose Torres²  Adam Aguirre²  Margot Paulino¹  Cristian O. Salas⁴  Jean Jacques Vanden Eynde³  Annie Mayence³ 

[1] Centro de Bioinformática Estructural-DETEMA, Facultad de Química, Universidad de la República, C.C. 1157 Montevideo, Uruguay; E-Mail:;Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile; E-Mails:Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile;;Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile; E-Mails:

关键词: antitumor;    purine derivatives;    apoptosis;    pharmacophoric model;   

DOI  :  10.3390/molecules20046808

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.