Abstract
Background: Protease activated receptor-1 (PAR1) is a G-coupled receptor activated by α-thrombin and other proteases. Several reports have demonstrated the PAR1 involvement in tumorigenesis and tumor progression. In order to investigate on potential use of PAR1 antagonists as antiproliferative agents.
Aims: We have identified a series of arylpiperazine derivatives acting as PAR1 antagonists; the selected molecules have been evaluated for their antiproliferative properties. Method: All the compounds inhibited the growth of a panel of cell lines expressing PAR1; two of them, compounds 13 and 15, were able to inhibit, in a dose dependent manner, the growth of the selected cell lines with the lowest IC50 values, and were further characterized to define the mechanism responsible for the observed antiproliferative effect. Result: This study directed us to the identification of two interesting leads that may help to further validate PAR1 as an important therapeutic target for cancer treatment.Keywords: Antagonists, antiproliferative agents, arylpiperazines, protease activated receptor-1.
Graphical Abstract
Anti-Cancer Agents in Medicinal Chemistry
Title:Synthesis of Arylpiperazine Derivatives as Protease Activated Receptor 1 Antagonists and Their Evaluation as Antiproliferative Agents
Volume: 17 Issue: 7
Author(s): Andrea Ilaria Zotti, Elena Di Gennaro, Angela Corvino, Francesco Frecentese, Elisa Magli, Elisa Perissutti, Giuseppe Cirino, Fiorentina Roviezzo, Manuela Terranova-Barberio, Federica Iannelli, Giuseppe Caliendo, Vincenzo Santagada, Ferdinando Fiorino, Alfredo Budillon and Beatrice Severino*
Affiliation:
- Department of Pharmacy, University of Naples ,Italy
Keywords: Antagonists, antiproliferative agents, arylpiperazines, protease activated receptor-1.
Abstract: Background: Protease activated receptor-1 (PAR1) is a G-coupled receptor activated by α-thrombin and other proteases. Several reports have demonstrated the PAR1 involvement in tumorigenesis and tumor progression. In order to investigate on potential use of PAR1 antagonists as antiproliferative agents.
Aims: We have identified a series of arylpiperazine derivatives acting as PAR1 antagonists; the selected molecules have been evaluated for their antiproliferative properties. Method: All the compounds inhibited the growth of a panel of cell lines expressing PAR1; two of them, compounds 13 and 15, were able to inhibit, in a dose dependent manner, the growth of the selected cell lines with the lowest IC50 values, and were further characterized to define the mechanism responsible for the observed antiproliferative effect. Result: This study directed us to the identification of two interesting leads that may help to further validate PAR1 as an important therapeutic target for cancer treatment.Export Options
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Cite this article as:
Zotti Ilaria Andrea, Di Gennaro Elena, Corvino Angela, Frecentese Francesco, Magli Elisa, Perissutti Elisa, Cirino Giuseppe, Roviezzo Fiorentina, Terranova-Barberio Manuela, Iannelli Federica, Caliendo Giuseppe, Santagada Vincenzo, Fiorino Ferdinando, Budillon Alfredo and Severino Beatrice*, Synthesis of Arylpiperazine Derivatives as Protease Activated Receptor 1 Antagonists and Their Evaluation as Antiproliferative Agents, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (7) . https://dx.doi.org/10.2174/1871520616666160926120904
DOI https://dx.doi.org/10.2174/1871520616666160926120904 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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