Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy

Naoki Kudou; Akira Taniguchi; Kenji Sugimoto; Yuji Matsuya; Masashi Kawasaki; Naoki Toyooka; Chika Miyoshi; Suresh Awale; Dya Fita Dibwe; Hiroyasu Esumi; Shigetoshi Kadota; Yasuhiro Tezuka

doi:10.1016/j.ejmech.2012.11.031

Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy

Naoki Kudou, Akira Taniguchi, Kenji Sugimoto, Yuji Matsuya, Masashi Kawasaki, Naoki Toyooka^*, Chika Miyoshi, Suresh Awale, Dya Fita Dibwe, Hiroyasu Esumi, Shigetoshi Kadota, Yasuhiro Tezuka

^*Corresponding author for this work

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

39 Scopus citations

Abstract

A series of new (-)-arctigenin derivatives with variably modified O-alkyl groups were synthesized and their preferential cytotoxicity was evaluated against human pancreatic cancer cell line PANC-1 under nutrient-deprived conditions. The results showed that monoethoxy derivative 4i (PC₅₀, 0.49 μM), diethoxy derivative 4h (PC₅₀, 0.66 μM), and triethoxy derivative 4m (PC₅₀, 0.78 μM) showed the preferential cytotoxicities under nutrient-deprived conditions, which were identical to or more potent than (-)-arctigenin (1) (PC₅₀, 0.80 μM). Among them, we selected the triethoxy derivative 4m and examined its in vivo antitumor activity using a mouse xenograft model. Triethoxy derivative 4m exhibited also in vivo antitumor activity with the potency identical to or slightly more than (-)-arctigenin (1). These results would suggest that a modification of (-)-arctigenin structure could lead to a new drug based on the antiausterity strategy.

Original language	English
Pages (from-to)	76-88
Number of pages	13
Journal	European Journal of Medicinal Chemistry
Volume	60
DOIs	https://doi.org/10.1016/j.ejmech.2012.11.031
State	Published - 2013/02

Keywords

(-)-Arctigenin derivatives
Antiausteric activity
Pancreatic cancer
Synthesis

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

UN SDGs

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

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10.1016/j.ejmech.2012.11.031

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@article{0fdcba7f959e43a392f0d13cf6fb4e5f,

title = "Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy",

abstract = "A series of new (-)-arctigenin derivatives with variably modified O-alkyl groups were synthesized and their preferential cytotoxicity was evaluated against human pancreatic cancer cell line PANC-1 under nutrient-deprived conditions. The results showed that monoethoxy derivative 4i (PC50, 0.49 μM), diethoxy derivative 4h (PC50, 0.66 μM), and triethoxy derivative 4m (PC50, 0.78 μM) showed the preferential cytotoxicities under nutrient-deprived conditions, which were identical to or more potent than (-)-arctigenin (1) (PC50, 0.80 μM). Among them, we selected the triethoxy derivative 4m and examined its in vivo antitumor activity using a mouse xenograft model. Triethoxy derivative 4m exhibited also in vivo antitumor activity with the potency identical to or slightly more than (-)-arctigenin (1). These results would suggest that a modification of (-)-arctigenin structure could lead to a new drug based on the antiausterity strategy.",

keywords = "(-)-Arctigenin derivatives, Antiausteric activity, Pancreatic cancer, Synthesis",

author = "Naoki Kudou and Akira Taniguchi and Kenji Sugimoto and Yuji Matsuya and Masashi Kawasaki and Naoki Toyooka and Chika Miyoshi and Suresh Awale and Dibwe, {Dya Fita} and Hiroyasu Esumi and Shigetoshi Kadota and Yasuhiro Tezuka",

note = "Funding Information: This work was supported in part by grants from the Ministry of Health and Welfare for the Third-Term Comprehensive 10-Year Strategy for Cancer Control and by Grant-in-Aid for Scientific Research (C) (No. 22590098 ) from Japan Society for the Promotion of Science (JSPS) . ",

year = "2013",

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doi = "10.1016/j.ejmech.2012.11.031",

language = "英語",

volume = "60",

pages = "76--88",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

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TY - JOUR

T1 - Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy

AU - Kudou, Naoki

AU - Taniguchi, Akira

AU - Sugimoto, Kenji

AU - Matsuya, Yuji

AU - Kawasaki, Masashi

AU - Toyooka, Naoki

AU - Miyoshi, Chika

AU - Awale, Suresh

AU - Dibwe, Dya Fita

AU - Esumi, Hiroyasu

AU - Kadota, Shigetoshi

AU - Tezuka, Yasuhiro

N1 - Funding Information: This work was supported in part by grants from the Ministry of Health and Welfare for the Third-Term Comprehensive 10-Year Strategy for Cancer Control and by Grant-in-Aid for Scientific Research (C) (No. 22590098 ) from Japan Society for the Promotion of Science (JSPS) .

PY - 2013/2

Y1 - 2013/2

N2 - A series of new (-)-arctigenin derivatives with variably modified O-alkyl groups were synthesized and their preferential cytotoxicity was evaluated against human pancreatic cancer cell line PANC-1 under nutrient-deprived conditions. The results showed that monoethoxy derivative 4i (PC50, 0.49 μM), diethoxy derivative 4h (PC50, 0.66 μM), and triethoxy derivative 4m (PC50, 0.78 μM) showed the preferential cytotoxicities under nutrient-deprived conditions, which were identical to or more potent than (-)-arctigenin (1) (PC50, 0.80 μM). Among them, we selected the triethoxy derivative 4m and examined its in vivo antitumor activity using a mouse xenograft model. Triethoxy derivative 4m exhibited also in vivo antitumor activity with the potency identical to or slightly more than (-)-arctigenin (1). These results would suggest that a modification of (-)-arctigenin structure could lead to a new drug based on the antiausterity strategy.

AB - A series of new (-)-arctigenin derivatives with variably modified O-alkyl groups were synthesized and their preferential cytotoxicity was evaluated against human pancreatic cancer cell line PANC-1 under nutrient-deprived conditions. The results showed that monoethoxy derivative 4i (PC50, 0.49 μM), diethoxy derivative 4h (PC50, 0.66 μM), and triethoxy derivative 4m (PC50, 0.78 μM) showed the preferential cytotoxicities under nutrient-deprived conditions, which were identical to or more potent than (-)-arctigenin (1) (PC50, 0.80 μM). Among them, we selected the triethoxy derivative 4m and examined its in vivo antitumor activity using a mouse xenograft model. Triethoxy derivative 4m exhibited also in vivo antitumor activity with the potency identical to or slightly more than (-)-arctigenin (1). These results would suggest that a modification of (-)-arctigenin structure could lead to a new drug based on the antiausterity strategy.

KW - (-)-Arctigenin derivatives

KW - Antiausteric activity

KW - Pancreatic cancer

KW - Synthesis

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SN - 0223-5234

VL - 60

SP - 76

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JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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