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.

Camilla Pecoraro, F.S. (2024). Synthesis and biological evaluation of a new class of azole urea compounds as Akt inhibitors with promising anticancer activity in pancreatic cancer models. BIOORGANIC CHEMISTRY, 153 [10.1016/j.bioorg.2024.107959].

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

Camilla Pecoraro;Daniela Carbone;Stella Cascioferro
;
Elisa Giovannetti
;
Patrizia Diana;Barbara Parrino
2024-12-01

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.
dic-2024
Camilla Pecoraro, F.S. (2024). Synthesis and biological evaluation of a new class of azole urea compounds as Akt inhibitors with promising anticancer activity in pancreatic cancer models. BIOORGANIC CHEMISTRY, 153 [10.1016/j.bioorg.2024.107959].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/669445
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