Discovery of New Aminosubstituted Pyrrolopyrimidines with Antiproliferative Activity Against Breast Cancer Cells and Investigation of their Effect Towards the PI3Kα Enzyme

Author(s): Konstantinos Daniilides, Nikolaos Lougiakis, Thomas Evangelidis, Ioannis K. Kostakis, Nicole Pouli, Panagiotis Marakos*, Emmanuel Mikros, Alexios-Leandros Skaltsounis, Stephane Bach, Blandine Baratte, Sandrine Ruchaud, Valia Karamani, Alexandra Papafotika, Savvas Christoforidis, Orestis Argyros, Eva Kouvari, Constantin Tamvakopoulos

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 17 , Issue 7 , 2017

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Graphical Abstract:


Objective: A series of novel 2,4-diaminosubstituted pyrrolo[3,2-d]pyrimidines was synthesized together with their corresponding 7-phenyl or 7-isopropyl counterparts.

Results: Among the target derivatives, the 7-substituted analogues exhibited interesting cytotoxic activity against a panel of PI3Kα related human breast cancer cell lines, namely MCF7, T47D, MDA-MB-231 and HCC1954. Selected compounds were tested for potential PI3Kα inhibitory activity as well as for their cytotoxic effect in prostate cancer cell lines (DU145 and PC3).

Conclusion: Derivatives bearing a specific substitution pattern consisting of 7-phenyl as well as a 2-(4- aminocyclohexylamino) moiety (16c, 16f) display kinase inhibitory activity, elucidated on the basis of molecular simulation studies, which revealed their interaction with the DFG motif of the kinase.

Keywords: 9-deazapurine, pyrrolo[3, 2-d]pyrimidine, cytotoxicity, breast cancer, PI3K inhibition, docking scoring, molecular dynamics.

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Article Details

Year: 2017
Published on: 07 December, 2016
Page: [990 - 1002]
Pages: 13
DOI: 10.2174/1871520616666161207143450
Price: $65

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