Generation of a poly-functionalized indolizine scaffold and its anticancer activity in pancreatic cancer cells

Yechan Lee, Dirgha Raj Joshi, Wan Namkung, Ikyon Kim

Research output: Contribution to journalArticlepeer-review

Abstract

A highly efficient domino [4 + 2] annulation process was employed to construct a novel indolizine chemical scaffold. Biological investigation led us to identify 6w as a potent anticancer agent. 6w significantly inhibited cell viability in BxPC3 pancreatic cancer, MCF7 breast cancer, and PC3 prostate cancer cell lines with IC50 values of 0.47 ± 0.04, 1.82 ± 0.08 and 2.68 ± 0.08 µM, respectively. Remarkably, 6w showed a weak effect on cell viability of nontumorigenic human keratinocyte cell line HaCaT compared to the above three types of cancer cells. 6w most potently inhibited cell viability of BxPC3 cells, and 6w also potently reduced cell migration and induced apoptosis in BxPC3 cells through activation of caspase-3 and cleavage of PARP in a dose-dependent manner. These results suggest that 6w can be used for the development of potential anticancer drugs for the treatment of pancreatic cancer.

Original languageEnglish
Article number105877
JournalBioorganic Chemistry
Volume126
DOIs
Publication statusPublished - 2022 Sep

Bibliographical note

Funding Information:
We thank the National Research Foundation of Korea ( NRF-2018R1A6A1A03023718 and NRF-2020R1A2C2005961 ) for generous financial support.

Publisher Copyright:
© 2022 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

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