Novel anti-prostate cancer scaffold identified by the combination of in silico and cell-based assays targeting the PI3K-AKT-mTOR pathway

  • Bioorg Med Chem Lett. 2017 Sep 1;27(17):4001-4006. doi: 10.1016/j.bmcl.2017.07.061.
Marta Érica Saidel  1 ,  Karen C Dos Santos  1 ,  Luís F P Nagano  1 ,  Carlos Alberto Montanari  1 ,  Andrei Leitão  2
Affiliations
  • 1. Medicinal Chemistry Group (NEQUIMED), São Carlos Institute of Chemistry, University of São Paulo, Brazil.
  • 2. Medicinal Chemistry Group (NEQUIMED), São Carlos Institute of Chemistry, University of São Paulo, Brazil. Electronic address: [email protected].
PMID: 28774426 DOI: 10.1016/j.bmcl.2017.07.061
Abstract

Phenotypic assays were performed in prostate Cancer cell lines to describe the biological activity of PI3K-AKT-mTOR pathway inhibitors retrieved from the virtual screening initiative. These novel chemicals share in common the aminopyridine scaffold, hitting PC-3 cells in macromolar range, with selectivity index over fibroblast cell lines. Moreover, a preliminary study of the mode of action by flow cytometry assay pointed out that these compounds had a rapamycin-like response for the PI3K-AKT-mTOR pathway modulation.

Keywords
Cell-based assays; In silico screening; PI3K-AKT-mTOR pathway inhibitors; Prostate cancer.