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Molecules 2015, 20(4), 6808-6826; doi:10.3390/molecules20046808

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

1
Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile
2
Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile
3
Centro de Bioinformática Estructural-DETEMA, Facultad de Química, Universidad de la República, C.C. 1157 Montevideo, Uruguay
*
Author to whom correspondence should be addressed.
Academic Editors: Jean Jacques Vanden Eynde, Annie Mayence and Tien L. Huang
Received: 4 March 2015 / Revised: 9 April 2015 / Accepted: 10 April 2015 / Published: 15 April 2015
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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. View Full-Text
Keywords: antitumor; purine derivatives; apoptosis; pharmacophoric model antitumor; purine derivatives; apoptosis; pharmacophoric model
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Calderón-Arancibia, J.; Espinosa-Bustos, C.; Cañete-Molina, Á.; Tapia, R.A.; Faúndez, M.; Torres, M.J.; Aguirre, A.; Paulino, M.; Salas, C.O. Synthesis and Pharmacophore Modelling of 2,6,9-Trisubstituted Purine Derivatives and Their Potential Role as Apoptosis-Inducing Agents in Cancer Cell Lines. Molecules 2015, 20, 6808-6826.

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