2. Academic Validation
  3. Development of potent isoflavone-based formyl peptide receptor 1 (FPR1) antagonists and their effects in gastric cancer cell models

Development of potent isoflavone-based formyl peptide receptor 1 (FPR1) antagonists and their effects in gastric cancer cell models

  • Eur J Med Chem. 2023 Oct 4:261:115854. doi: 10.1016/j.ejmech.2023.115854.
Fabio Francavilla 1,  Federica Sarcina 1,  Igor A Schepetkin 2,  Lilya N Kirpotina 2,  Marialessandra Contino 1,  Annalisa Schirizzi 3,  Giampiero De Leonardis 3,  Andrei I Khlebnikov 4,  Rosalba D'Alessandro 3,  Mark T Quinn 2,  Enza Lacivita 5,  Marcello Leopoldo 1
Affiliations

Affiliations

  • 1 Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, via Orabona 4, 70125, Bari, Italy.
  • 2 Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT, 59717, USA.
  • 3 Laboratory of Experimental Oncology, National Institute of Gastroenterology - IRCCS "Saverio de Bellis", Research Hospital, 70013, Castellana Grotte (BA), Italy.
  • 4 Kizhner Research Center, Tomsk Polytechnic University, Tomsk, 634050, Russia.
  • 5 Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, via Orabona 4, 70125, Bari, Italy. Electronic address: enza.lacivita@uniba.it.
PMID: 37839346 DOI: 10.1016/j.ejmech.2023.115854
Abstract

Formyl peptide receptor-1 (FPR1) is a G protein-coupled chemoattractant receptor that plays a crucial role in the trafficking of leukocytes into the sites of Bacterial infection and inflammation. Recently, FPR1 was shown to be expressed in different types of tumor cells and could play a significant role in tumor growth and invasiveness. Starting from the previously reported FPR1 antagonist 4, we have designed a new series of 4H-chromen-2-one derivatives that exhibited a substantial increase in FPR1 antagonist potency. Docking studies identified the key interactions for antagonist activity. The most potent compounds in this series (24a and 25b) were selected to study the effects of the pharmacological blockade of FPR1 in NCl-N87 and AGS gastric Cancer cells. Both compounds potently inhibited cell growth through a combined effect on cell proliferation and Apoptosis and reduced cell migration, while inducing an increase in angiogenesis, thus suggesting that FPR1 could play a dual role as oncogene and onco-suppressor.

Keywords

4H-chromen-2-one derivatives; Cell growth; Docking studies; FPR1; Gastric cancer.

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