Design and synthesis of novel pipernonaline derivatives as anti-austerity agents against human pancreatic cancer PANC-1 cells

Takuya Okada*, Yuri Chino, Keita Yokoyama, Yuki Fujihashi, Nguyễn Duy Phan, Juthamart Maneenet, Lanke Prudhvi, Suresh Awale, Naoki Toyooka

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Pipernonaline (1), one of the components of the spice pepper, preferentially reduced the survival of human pancreatic cancer PANC-1 cells under nutrient-deprived conditions with a PC50 value of 7.2 μM, suggesting that 1 could potentially lead to the development of new anticancer agents based on the anti-austerity strategy. We have synthesized a total of 31 pipernonaline derivatives, revealing clear structure–activity relationships. Compound 9, which showed the strongest preferential cytotoxicity among synthesized derivatives, inhibited Akt activation and cancer cell migration, making it an extremely promising candidate compound for new pancreatic cancer agents based on the anti-austerity strategy.

Original languageEnglish
Article number116963
JournalBioorganic and Medicinal Chemistry
Volume71
DOIs
StatePublished - 2022/10/01

Keywords

  • Anti-austerity strategy
  • Pancreatic cancer
  • Pipernonaline
  • Structure-activity relationship

ASJC Scopus subject areas

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

Fingerprint

Dive into the research topics of 'Design and synthesis of novel pipernonaline derivatives as anti-austerity agents against human pancreatic cancer PANC-1 cells'. Together they form a unique fingerprint.

Cite this