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.
Graphical Abstract
Anti-Cancer Agents in Medicinal Chemistry
Title:Discovery of New Aminosubstituted Pyrrolopyrimidines with Antiproliferative Activity Against Breast Cancer Cells and Investigation of their Effect Towards the PI3Kα Enzyme
Volume: 17 Issue: 7
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 and Constantin Tamvakopoulos
Affiliation:
- Division of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Zografou,Greece
Keywords: 9-deazapurine, pyrrolo[3, 2-d]pyrimidine, cytotoxicity, breast cancer, PI3K inhibition, docking scoring, molecular dynamics.
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.Export Options
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Cite this article as:
Daniilides Konstantinos, Lougiakis Nikolaos, Evangelidis Thomas, Kostakis K. Ioannis, Pouli Nicole, Marakos Panagiotis*, Mikros Emmanuel, Skaltsounis Alexios-Leandros, Bach Stephane, Baratte Blandine, Ruchaud Sandrine, Karamani Valia, Papafotika Alexandra, Christoforidis Savvas, Argyros Orestis, Kouvari Eva and Tamvakopoulos Constantin, Discovery of New Aminosubstituted Pyrrolopyrimidines with Antiproliferative Activity Against Breast Cancer Cells and Investigation of their Effect Towards the PI3Kα Enzyme, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (7) . https://dx.doi.org/10.2174/1871520616666161207143450
DOI https://dx.doi.org/10.2174/1871520616666161207143450 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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