Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents

Kangjia Du; Wantong Ma; Chengjie Yang; Zhongkun Zhou; Shujian Hu; Yanan Tian; Hao Zhang; Yunhao Ma; Xinrong Jiang; Hongmei Zhu; Huanxiang Liu; Peng Chen; Yingqian Liu

doi:10.1080/14756366.2022.2065672

Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents

Kangjia Du, Wantong Ma, Chengjie Yang, Zhongkun Zhou, Shujian Hu, Yanan Tian, Hao Zhang, Yunhao Ma, Xinrong Jiang, Hongmei Zhu, Huanxiang Liu, Peng Chen, Yingqian Liu

Lanzhou University

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

11 Citations (Scopus)

Abstract

A series of novel derivatives of isaindigotone, which comes from the root of isaits indinatca Fort, were synthesised (Compound 1–26). Four human gastrointestinal cancer cells (HCT116, PANC-1, SMMC-7721, and AGS) were employed to evaluate the anti-proliferative activity. Among them, Compound 6 displayed the most effective inhibitory activity on AGS cells with an IC₅₀ (50% inhibitory concentration) value of 2.2 μM. The potential mechanism study suggested that Compound 6 induced apoptosis in AGS cells. The collapse of mitochondrial membrane potential (MMP) in AGS cells was proved. In docking analysis, good affinity interaction between Compound 6 and AKT1 was discovered. Treatment of AGS cells with Compound 6 also resulted in significant suppression of PI3K/AKT/mTOR signal pathway. The collapse of MMP and suppression of PI3K/AKT/mTOR signal pathway may be responsible for induction of apoptosis. This derivative Compound 6 could be useful as an underlying anti-tumour agent for treatment of gastric cancer.

Original language	English
Pages (from-to)	1212-1226
Number of pages	15
Journal	Journal of Enzyme Inhibition and Medicinal Chemistry
Volume	37
Issue number	1
DOIs	https://doi.org/10.1080/14756366.2022.2065672
Publication status	Published - 2022
Externally published	Yes

Keywords

Isaindigotone
MMP
PI3K/AKT/mTOR
apoptosis
cytotoxicity

UN SDGs

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

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10.1080/14756366.2022.2065672

Cite this

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title = "Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents",

abstract = "A series of novel derivatives of isaindigotone, which comes from the root of isaits indinatca Fort, were synthesised (Compound 1–26). Four human gastrointestinal cancer cells (HCT116, PANC-1, SMMC-7721, and AGS) were employed to evaluate the anti-proliferative activity. Among them, Compound 6 displayed the most effective inhibitory activity on AGS cells with an IC50 (50% inhibitory concentration) value of 2.2 μM. The potential mechanism study suggested that Compound 6 induced apoptosis in AGS cells. The collapse of mitochondrial membrane potential (MMP) in AGS cells was proved. In docking analysis, good affinity interaction between Compound 6 and AKT1 was discovered. Treatment of AGS cells with Compound 6 also resulted in significant suppression of PI3K/AKT/mTOR signal pathway. The collapse of MMP and suppression of PI3K/AKT/mTOR signal pathway may be responsible for induction of apoptosis. This derivative Compound 6 could be useful as an underlying anti-tumour agent for treatment of gastric cancer.",

keywords = "Isaindigotone, MMP, PI3K/AKT/mTOR, apoptosis, cytotoxicity",

author = "Kangjia Du and Wantong Ma and Chengjie Yang and Zhongkun Zhou and Shujian Hu and Yanan Tian and Hao Zhang and Yunhao Ma and Xinrong Jiang and Hongmei Zhu and Huanxiang Liu and Peng Chen and Yingqian Liu",

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year = "2022",

doi = "10.1080/14756366.2022.2065672",

language = "English",

volume = "37",

pages = "1212--1226",

journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",

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TY - JOUR

T1 - Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents

AU - Du, Kangjia

AU - Ma, Wantong

AU - Yang, Chengjie

AU - Zhou, Zhongkun

AU - Hu, Shujian

AU - Tian, Yanan

AU - Zhang, Hao

AU - Ma, Yunhao

AU - Jiang, Xinrong

AU - Zhu, Hongmei

AU - Liu, Huanxiang

AU - Chen, Peng

AU - Liu, Yingqian

PY - 2022

Y1 - 2022

N2 - A series of novel derivatives of isaindigotone, which comes from the root of isaits indinatca Fort, were synthesised (Compound 1–26). Four human gastrointestinal cancer cells (HCT116, PANC-1, SMMC-7721, and AGS) were employed to evaluate the anti-proliferative activity. Among them, Compound 6 displayed the most effective inhibitory activity on AGS cells with an IC50 (50% inhibitory concentration) value of 2.2 μM. The potential mechanism study suggested that Compound 6 induced apoptosis in AGS cells. The collapse of mitochondrial membrane potential (MMP) in AGS cells was proved. In docking analysis, good affinity interaction between Compound 6 and AKT1 was discovered. Treatment of AGS cells with Compound 6 also resulted in significant suppression of PI3K/AKT/mTOR signal pathway. The collapse of MMP and suppression of PI3K/AKT/mTOR signal pathway may be responsible for induction of apoptosis. This derivative Compound 6 could be useful as an underlying anti-tumour agent for treatment of gastric cancer.

AB - A series of novel derivatives of isaindigotone, which comes from the root of isaits indinatca Fort, were synthesised (Compound 1–26). Four human gastrointestinal cancer cells (HCT116, PANC-1, SMMC-7721, and AGS) were employed to evaluate the anti-proliferative activity. Among them, Compound 6 displayed the most effective inhibitory activity on AGS cells with an IC50 (50% inhibitory concentration) value of 2.2 μM. The potential mechanism study suggested that Compound 6 induced apoptosis in AGS cells. The collapse of mitochondrial membrane potential (MMP) in AGS cells was proved. In docking analysis, good affinity interaction between Compound 6 and AKT1 was discovered. Treatment of AGS cells with Compound 6 also resulted in significant suppression of PI3K/AKT/mTOR signal pathway. The collapse of MMP and suppression of PI3K/AKT/mTOR signal pathway may be responsible for induction of apoptosis. This derivative Compound 6 could be useful as an underlying anti-tumour agent for treatment of gastric cancer.

KW - Isaindigotone

KW - MMP

KW - PI3K/AKT/mTOR

KW - apoptosis

KW - cytotoxicity

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DO - 10.1080/14756366.2022.2065672

M3 - Article

C2 - 35450499

AN - SCOPUS:85128681253

SN - 1475-6366

VL - 37

SP - 1212

EP - 1226

JO - Journal of Enzyme Inhibition and Medicinal Chemistry

JF - Journal of Enzyme Inhibition and Medicinal Chemistry

IS - 1

ER -

Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents

Abstract

Keywords

UN SDGs

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Study Findings on Gastric Cancer Are Outlined in Reports from Lanzhou University (Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents)

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Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents

Abstract

Keywords

UN SDGs

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Study Findings on Gastric Cancer Are Outlined in Reports from Lanzhou University (Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents)

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