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

^*Corresponding author for this work

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

11 Scopus citations

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.

Original language	English
Article number	126964
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	30
Issue number	7
DOIs	https://doi.org/10.1016/j.bmcl.2020.126964
State	Published - 2020/04/01

Keywords

Antiausterity agent
Drug discovery
Guggulsterone
PANC-1
Pancreatic cancer
Preferential cytotoxicity
Steroid

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

UN SDGs

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

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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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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