Synthesis of guggulsterone derivatives as potential anti-austerity agents against PANC-1 human pancreatic cancer cells

Aki Kohyama; Rei Yokoyama; Dya Fita Dibwe; Sahar El-Mekkawy; Meselhy R. Meselhy; Suresh Awale; Yuji Matsuya

doi:10.1016/j.bmcl.2020.126964

Synthesis of guggulsterone derivatives as potential anti-austerity agents against PANC-1 human pancreatic cancer cells

Aki Kohyama, Rei Yokoyama, Dya Fita Dibwe, Sahar El-Mekkawy, Meselhy R. Meselhy, Suresh Awale^*, Yuji Matsuya

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研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

11 被引用数 (Scopus)

抄録

E- and Z-guggulsterones and nine guggulsterone derivatives (GSDs) were synthesized and evaluated for their preferential cytotoxicity against human PANC-1 cell in nutrient deprived medium utilizing antiausterity strategy. Among the synthesized compounds, GSD-1 and GSD-7 showed potent cytotoxicity against PANC-1 cells under nutrient-deprived conditions in a concentration dependent manner, with a PC₅₀ value of 1.6 μM and 3.2 μM, respectively. The effect of GSD-1 and GSD-7 was further evaluated in a real time using live cell imaging. Both of these compounds altered PANC-1 cell morphology, leading to cell death at sub micromolar concentration range. GSD-1 and GSD-7 also inhibited PANC-1 cell colony formation in a concentration-dependent manner. GSD-1 and GSD-7 are lead structure for the anti-austerity drug development.

本文言語	英語
論文番号	126964
ジャーナル	Bioorganic and Medicinal Chemistry Letters
巻	30
号	7
DOI	https://doi.org/10.1016/j.bmcl.2020.126964
出版ステータス	出版済み - 2020/04/01

ASJC Scopus 主題領域

生化学
分子医療
分子生物学
薬科学
創薬
臨床生化学
有機化学

UN SDG

この成果は、次の持続可能な開発目標に貢献しています

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10.1016/j.bmcl.2020.126964

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@article{96fb4b52704a477d8135f5a1e0700a90,

title = "Synthesis of guggulsterone derivatives as potential anti-austerity agents against PANC-1 human pancreatic cancer cells",

abstract = "E- and Z-guggulsterones and nine guggulsterone derivatives (GSDs) were synthesized and evaluated for their preferential cytotoxicity against human PANC-1 cell in nutrient deprived medium utilizing antiausterity strategy. Among the synthesized compounds, GSD-1 and GSD-7 showed potent cytotoxicity against PANC-1 cells under nutrient-deprived conditions in a concentration dependent manner, with a PC50 value of 1.6 μM and 3.2 μM, respectively. The effect of GSD-1 and GSD-7 was further evaluated in a real time using live cell imaging. Both of these compounds altered PANC-1 cell morphology, leading to cell death at sub micromolar concentration range. GSD-1 and GSD-7 also inhibited PANC-1 cell colony formation in a concentration-dependent manner. GSD-1 and GSD-7 are lead structure for the anti-austerity drug development.",

keywords = "Antiausterity agent, Drug discovery, Guggulsterone, PANC-1, Pancreatic cancer, Preferential cytotoxicity, Steroid",

author = "Aki Kohyama and Rei Yokoyama and Dibwe, {Dya Fita} and Sahar El-Mekkawy and Meselhy, {Meselhy R.} and Suresh Awale and Yuji Matsuya",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",

year = "2020",

month = apr,

day = "1",

doi = "10.1016/j.bmcl.2020.126964",

language = "英語",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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TY - JOUR

T1 - Synthesis of guggulsterone derivatives as potential anti-austerity agents against PANC-1 human pancreatic cancer cells

AU - Kohyama, Aki

AU - Yokoyama, Rei

AU - Dibwe, Dya Fita

AU - El-Mekkawy, Sahar

AU - Meselhy, Meselhy R.

AU - Awale, Suresh

AU - Matsuya, Yuji

PY - 2020/4/1

Y1 - 2020/4/1

N2 - E- and Z-guggulsterones and nine guggulsterone derivatives (GSDs) were synthesized and evaluated for their preferential cytotoxicity against human PANC-1 cell in nutrient deprived medium utilizing antiausterity strategy. Among the synthesized compounds, GSD-1 and GSD-7 showed potent cytotoxicity against PANC-1 cells under nutrient-deprived conditions in a concentration dependent manner, with a PC50 value of 1.6 μM and 3.2 μM, respectively. The effect of GSD-1 and GSD-7 was further evaluated in a real time using live cell imaging. Both of these compounds altered PANC-1 cell morphology, leading to cell death at sub micromolar concentration range. GSD-1 and GSD-7 also inhibited PANC-1 cell colony formation in a concentration-dependent manner. GSD-1 and GSD-7 are lead structure for the anti-austerity drug development.

AB - E- and Z-guggulsterones and nine guggulsterone derivatives (GSDs) were synthesized and evaluated for their preferential cytotoxicity against human PANC-1 cell in nutrient deprived medium utilizing antiausterity strategy. Among the synthesized compounds, GSD-1 and GSD-7 showed potent cytotoxicity against PANC-1 cells under nutrient-deprived conditions in a concentration dependent manner, with a PC50 value of 1.6 μM and 3.2 μM, respectively. The effect of GSD-1 and GSD-7 was further evaluated in a real time using live cell imaging. Both of these compounds altered PANC-1 cell morphology, leading to cell death at sub micromolar concentration range. GSD-1 and GSD-7 also inhibited PANC-1 cell colony formation in a concentration-dependent manner. GSD-1 and GSD-7 are lead structure for the anti-austerity drug development.

KW - Antiausterity agent

KW - Drug discovery

KW - Guggulsterone

KW - PANC-1

KW - Pancreatic cancer

KW - Preferential cytotoxicity

KW - Steroid

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U2 - 10.1016/j.bmcl.2020.126964

DO - 10.1016/j.bmcl.2020.126964

M3 - 学術論文

C2 - 32057581

AN - SCOPUS:85079191384

SN - 0960-894X

VL - 30

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 7

M1 - 126964

ER -

Synthesis of guggulsterone derivatives as potential anti-austerity agents against PANC-1 human pancreatic cancer cells

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ASJC Scopus 主題領域

UN SDG

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