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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Synthesis of Arylpiperazine Derivatives as Protease Activated Receptor 1 Antagonists and Their Evaluation as Antiproliferative Agents

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*

Volume 17, Issue 7, 2017

Page: [973 - 981] Pages: 9

DOI: 10.2174/1871520616666160926120904

Price: $65

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

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