2. Academic Validation
  3. Synthesis and biological evaluation of a new class of azole urea compounds as Akt inhibitors with promising anticancer activity in pancreatic cancer models

Synthesis and biological evaluation of a new class of azole urea compounds as Akt inhibitors with promising anticancer activity in pancreatic cancer models

  • Bioorg Chem. 2024 Dec:153:107959. doi: 10.1016/j.bioorg.2024.107959.
Camilla Pecoraro 1,  Fabio Scianò 2,  Daniela Carbone 1,  Geng Xu 3,  Juan Deng 3,  Stella Cascioferro 4,  Elisa Giovannetti 5,  Patrizia Diana 1,  Barbara Parrino 1
Affiliations

Affiliations

  • 1 Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy.
  • 2 Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy; Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University, Amsterdam 1081 HV, The Netherlands.
  • 3 Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University, Amsterdam 1081 HV, The Netherlands.
  • 4 Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy. Electronic address: stellamaria.cascioferro@unipa.it.
  • 5 Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University, Amsterdam 1081 HV, The Netherlands; Cancer Pharmacology Laboratory, Fondazione Pisana per la Scienza, Via Ferruccio Giovannini 13, 56017 Pisa, Italy. Electronic address: elisa.giovannetti@gmail.com.
PMID: 39556934 DOI: 10.1016/j.bioorg.2024.107959
Abstract

The PI3K/Akt pathway is crucial in numerous cellular functions such as cell growth, survival proliferation and movement in both normal and Cancer cells. It plays also a key role in epithelial-mesenchymal transitions and angiogenesis during the tumorigenesis processes. Since many transformative events in Cancer are driven by increased PI3K/Akt pathway signaling, Akt is considered a valuable target for developing new therapies against various tumor types, including pancreatic Cancer. This is because the PI3K/Akt/mTOR pathway is a key downstream effector of Ras, and Ras activation is the most prominent genetic alteration in pancreatic Cancer. Herein we report the synthesis and the biological evaluation of a new series of azole urea compounds that exhibited promising antiproliferative and antimigratory activities against pancreatic Cancer cells through an Akt inhibition mechanism. These effects were demonstrated using a variety of assays, including Sulforhodamine B, cell-cycle, wound-healing, and kinase activity, apotposis and ELISA assays. Additionally, the Anticancer properties of the most active compound in the series were confirmed in the 3D spheroid model of PATU-T cells.

Keywords

1,2,3-Triazole urea compounds; 3D spheroid model; Akt inhibitors; Anti-migratory activity; Pancreatic ductal adenocarcinoma.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-169413
    Akt Inhibitor
    Akt