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

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

doi:10.1016/j.bioorg.2022.105877

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

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

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

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 language	English
Article number	105877
Journal	Bioorganic Chemistry
Volume	126
DOIs	https://doi.org/10.1016/j.bioorg.2022.105877
Publication status	Published - 2022 Sept

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bioorg.2022.105877

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

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.",

author = "Yechan Lee and Joshi, {Dirgha Raj} and Wan Namkung and Ikyon Kim",

note = "Funding Information: We thank the National Research Foundation of Korea ( NRF-2018R1A6A1A03023718 and NRF-2020R1A2C2005961 ) for generous financial support. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2022",

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doi = "10.1016/j.bioorg.2022.105877",

language = "English",

volume = "126",

journal = "Bioorganic Chemistry",

issn = "0045-2068",

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AU - Lee, Yechan

AU - Joshi, Dirgha Raj

AU - Namkung, Wan

AU - Kim, Ikyon

N1 - Funding Information: We thank the National Research Foundation of Korea ( NRF-2018R1A6A1A03023718 and NRF-2020R1A2C2005961 ) for generous financial support. Publisher Copyright: © 2022 Elsevier Inc.

PY - 2022/9

Y1 - 2022/9

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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