Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator

Hyejin Ko; Seungchan An; Hongjun Jang; Sungjin Ahn; In Guk Park; Seok Young Hwang; Junpyo Gong; Soyeon Oh; Soo Yeon Kwak; Won Jun Choi; Hyoungsu Kim; Minsoo Noh

doi:10.4062/biomolther.2022.097

Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator

Hyejin Ko
, Seungchan An
, Hongjun Jang
, Sungjin Ahn
, In Guk Park
, Seok Young Hwang
, Junpyo Gong
, Soyeon Oh
, Soo Yeon Kwak
, Won Jun Choi
, Hyoungsu Kim
, Minsoo Noh

Department of Pharmacy

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

5 Scopus citations

Abstract

The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activat-ed receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesis-inducing activity by macakurzin C derivatives (2–7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadi-ponectinemia-related metabolic diseases.

Original language	English
Pages (from-to)	312-318
Number of pages	7
Journal	Biomolecules and Therapeutics
Volume	31
Issue number	3
DOIs	https://doi.org/10.4062/biomolther.2022.097
State	Published - May 2023

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Adiponectin
Human bone marrow mesenchymal stem cells
Macakurzin C derivative
Peroxisome proliferator-activated receptor
PPARα/γ dual modulator

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10.4062/biomolther.2022.097

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title = "Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator",

abstract = "The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activat-ed receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesis-inducing activity by macakurzin C derivatives (2–7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadi-ponectinemia-related metabolic diseases.",

keywords = "Adiponectin, Human bone marrow mesenchymal stem cells, Macakurzin C derivative, Peroxisome proliferator-activated receptor, PPARα/γ dual modulator",

author = "Hyejin Ko and Seungchan An and Hongjun Jang and Sungjin Ahn and Park, \{In Guk\} and Hwang, \{Seok Young\} and Junpyo Gong and Soyeon Oh and Kwak, \{Soo Yeon\} and Choi, \{Won Jun\} and Hyoungsu Kim and Minsoo Noh",

note = "Publisher Copyright: {\textcopyright} 2023 The Korean Society of Applied Pharmacology.",

year = "2023",

month = may,

doi = "10.4062/biomolther.2022.097",

language = "English",

volume = "31",

pages = "312--318",

journal = "Biomolecules and Therapeutics",

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publisher = "Korean Society of Applied Pharmacology",

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T1 - Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator

AU - Ko, Hyejin

AU - An, Seungchan

AU - Jang, Hongjun

AU - Ahn, Sungjin

AU - Park, In Guk

AU - Hwang, Seok Young

AU - Gong, Junpyo

AU - Oh, Soyeon

AU - Kwak, Soo Yeon

AU - Choi, Won Jun

AU - Kim, Hyoungsu

AU - Noh, Minsoo

PY - 2023/5

Y1 - 2023/5

N2 - The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activat-ed receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesis-inducing activity by macakurzin C derivatives (2–7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadi-ponectinemia-related metabolic diseases.

AB - The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activat-ed receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesis-inducing activity by macakurzin C derivatives (2–7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadi-ponectinemia-related metabolic diseases.

KW - Adiponectin

KW - Human bone marrow mesenchymal stem cells

KW - Macakurzin C derivative

KW - Peroxisome proliferator-activated receptor

KW - PPARα/γ dual modulator

UR - https://www.scopus.com/pages/publications/85159155843

U2 - 10.4062/biomolther.2022.097

DO - 10.4062/biomolther.2022.097

M3 - Article

AN - SCOPUS:85159155843

SN - 1976-9148

VL - 31

SP - 312

EP - 318

JO - Biomolecules and Therapeutics

JF - Biomolecules and Therapeutics

IS - 3

ER -

Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator

Abstract

UN SDGs

Keywords

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