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Updated: Jun 11, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Published on: January 22, 2019

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Design, synthesis, and biological evaluation of novel thiazole derivatives as PI3K/mTOR dual inhibitors

Samar I Faggal1, Yara El-Dash1, Amr Sonousi1,2

  • 1Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University Kasr El-Aini Street Cairo 11562 Egypt amr.motawi@pharma.cu.edu.eg.

RSC Medicinal Chemistry
|September 30, 2024
PubMed

Insights

New thiazole compounds show promise as dual PI3K/mTOR inhibitors for cancer therapy. Compounds 3b and 3e demonstrated significant antiproliferative and apoptotic effects in leukemia cells.

Area of Science:

  • Medicinal Chemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Targeting phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) pathways is a key strategy in anticancer drug development.
  • Developing dual PI3K/mTOR inhibitors offers a promising therapeutic approach for various cancers.

Purpose of the Study:

  • To design, synthesize, and evaluate novel thiazole compounds as potential dual PI3K/mTOR inhibitors.
  • To assess the antiproliferative and anti-apoptotic activities of these compounds in cancer cell lines.

Main Methods:

  • Synthesis of seventeen new thiazole compounds.
  • Antiproliferative screening against 60 cancer cell lines (National Cancer Institute).
  • In vitro enzyme inhibition assays against PI3Kα and mTOR.
  • Cell cycle analysis and apoptosis assays (caspase-3 levels).
  • Molecular docking studies.

Main Results:

  • Compounds 3b and 3e exhibited significant antiproliferative activity and were selected for further studies.
  • Compound 3b demonstrated PI3Kα inhibitory activity comparable to alpelisib and moderate mTOR inhibition.
  • Both compounds induced G0-G1 cell cycle arrest and increased apoptosis in HL-60(TB) leukemia cells.
  • Molecular docking supported the interaction of these compounds with PI3Kα/mTOR active sites.

Conclusions:

  • Compounds 3b and 3e are identified as potent PI3Kα/mTOR dual inhibitors.
  • These thiazole derivatives represent promising lead compounds for developing novel anticancer agents targeting the PI3K/mTOR pathway.

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