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Updated: Sep 21, 2025
Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 7, 2019
Generation of a poly-functionalized indolizine scaffold and its anticancer activity in pancreatic cancer cells
Yechan Lee1, Dirgha Raj Joshi2, Wan Namkung1
1College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85, Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea; Graduate Program of Industrial Pharmaceutical Science, Yonsei University, Incheon 21983, Republic of Korea.
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.
