Design and synthesis of functionalized coumarins as potential anti-austerity agents that eliminates cancer cells' tolerance to nutrition starvation

Suresh Awale*, Takahiro Okada, Dya Fita Dibwe, Takahiro Maruyama, Satoyuki Takahara, Takuya Okada, Satoshi Endo, Naoki Toyooka*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Human pancreatic tumor cells have inherent ability to tolerate nutrition starvation which enables them to survive in the hypovascular tumor microenvironment. Discovery of agents that selectively inhibit the cancer cells’ tolerance to nutrition starvation leading to cancer cell death is a new anti-austerity approach in anti-cancer drug discovery. A series of coumarins derivatives were synthesized and evaluated for their anti-austerity activity against PANC-1 human pancreatic cancer cell line. The compound 7-Hydroxy-2-oxo-2H-chromene-3-carboxylic acid (3-phenylpropyl)amide (2c)showed highly potent selective cytotoxicity against PANC-1 cells under nutrient-deprived conditions, with a PC50 value of 0.44 μM, without exhibiting toxicity in normal, nutrient-rich medium. Compound 2c caused dramatic alterations in PANC-1 cell morphology, leading to cell death. The compound 2c was found to inhibit PANC-1 cell migration and colony formation in a concentration-dependent manner. The compound 2c is a lead structure for the anti-austerity drug development against pancreatic cancer.

Original languageEnglish
Pages (from-to)1779-1784
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume29
Issue number14
DOIs
StatePublished - 2019/07/15

Keywords

  • Antiausterity agent
  • Coumarin
  • Drug discovery
  • PANC-1
  • Pancreatic cancer
  • Preferential cytotoxicity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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