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Updated: Jun 12, 2025

Preparation and In Vivo Use of an Activity-based Probe for N-acylethanolamine Acid Amidase
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Preparation and In Vivo Use of an Activity-based Probe for N-acylethanolamine Acid Amidase

Published on: November 23, 2016

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Structure-activity relationships study of N-ethylene glycol-comprising alkyl heterocyclic carboxamides against A549

Kaito Ohta1, Hiromi Ii2, Mei Takahashi1

  • 1Laboratory of Pharmaceutical Manufacturing Chemistry, Kyoto Pharmaceutical University, 1 Misasagi-Shichono-cho, Yamashina-ku, Kyoto, 607-8412, Japan.

Future Medicinal Chemistry
|September 19, 2024
PubMed

Insights

Researchers developed new mitochondrial inhibitors for non-small cell lung cancer. Analog 5e, with tetraethylene glycol units, showed significant tumor growth inhibition in vivo, indicating potential as a therapeutic agent.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Oncology

Background:

  • Cancer cells often rely on oxidative phosphorylation for energy.
  • Inhibiting this metabolic pathway presents a potential therapeutic strategy for cancer treatment.
  • Mitochondrial inhibitors are being investigated as novel anti-cancer agents.

Purpose of the Study:

  • To explore structure-activity relationships of novel N-ethylene glycol-comprising alkyl thiophene-3-carboxamide analogs.
  • To identify compounds with enhanced growth-inhibitory effects on non-small cell lung cancer cells.
  • To evaluate the therapeutic potential of these analogs as anti-cancer agents.

Main Methods:

  • Synthesis and evaluation of 13 analogs (5a-m) with variations in ethylene glycol units, heterocycles, and connecting groups.
  • Assessment of growth-inhibitory effects on A549 non-small cell lung cancer cells.
  • In vivo studies to evaluate tumor growth inhibition.

Main Results:

  • Increasing ethylene glycol units significantly enhanced inhibitory activity against cancer cells.
  • Some synthesized analogs activated adenosine monophosphate-activated protein kinase, similar to the parent compound.
  • Analog 5e, featuring tetraethylene glycol units, demonstrated significant inhibition of tumor growth in vivo.

Conclusions:

  • Analog 5, particularly analog 5e, shows promise as a potential therapeutic agent for non-small cell lung cancer.
  • The study highlights the importance of ethylene glycol chain length in optimizing mitochondrial inhibitor activity.
  • Further investigation into analog 5e is warranted for its development as a non-small cell lung cancer treatment.
Keywords:
AMP-activated protein kinaseantitumor agentsethylene glycolmitochondrial inhibitornon-small cell lung cancer cellsoxidative phosphorylationstructure–activity relationshipsthiophene-3-carboxamide

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