Novel thiazolidinedione derivatives with anti-obesity effects: Dual action as PTP1B inhibitors and PPAR-γ activators

Bharat Raj Bhattarai; Bhooshan Kafle; Ji Sun Hwang; Seung Wook Ham; Keun Hyeung Lee; Hwangseo Park; Inn Oc Han; Hyeongjin Cho

doi:10.1016/j.bmcl.2010.08.130

Novel thiazolidinedione derivatives with anti-obesity effects: Dual action as PTP1B inhibitors and PPAR-γ activators

Bharat Raj Bhattarai, Bhooshan Kafle, Ji Sun Hwang, Seung Wook Ham, Keun Hyeung Lee, Hwangseo Park, Inn Oc Han, Hyeongjin Cho

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

91 Scopus citations

Abstract

Benzylidene-2,4-thiazolidinedione derivatives with substitutions at both the ortho and para-positions of the phenyl group were synthesized as PTP1B inhibitors with IC₅₀ values in a low micromolar range. Compound 18l, the lowest, bore an IC₅₀ of 1.3 μM. In a peroxisome proliferator-activated receptor-γ (PPAR-γ) promoter reporter gene assay, 18l was found to activate the transcription of the reporter gene with potencies comparable to those of troglitazone, rosiglitazone, and pioglitazone. In vivo efficacy of 18l as an anti-obesity and hypoglycemic agent was evaluated in a mouse model system. Compound 18l significantly suppressed weight gain and significantly improved blood parameters such as TG, total cholesterol and NEFA without overt toxic effects.

Original language	English
Pages (from-to)	6758-6763
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2010.08.130
State	Published - 15 Nov 2010

Bibliographical note

Funding Information:
Support for this work was provided by Inha University. B. R. Bhattarai and B. Kafle were recipients of a BK21 fellowship.

Keywords

Anti-obesity
PPAR-γ activator
PTP1B inhibitor
Protein tyrosine phosphatase
Thiazolidinedione

UN SDGs

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

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10.1016/j.bmcl.2010.08.130

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title = "Novel thiazolidinedione derivatives with anti-obesity effects: Dual action as PTP1B inhibitors and PPAR-γ activators",

abstract = "Benzylidene-2,4-thiazolidinedione derivatives with substitutions at both the ortho and para-positions of the phenyl group were synthesized as PTP1B inhibitors with IC50 values in a low micromolar range. Compound 18l, the lowest, bore an IC50 of 1.3 μM. In a peroxisome proliferator-activated receptor-γ (PPAR-γ) promoter reporter gene assay, 18l was found to activate the transcription of the reporter gene with potencies comparable to those of troglitazone, rosiglitazone, and pioglitazone. In vivo efficacy of 18l as an anti-obesity and hypoglycemic agent was evaluated in a mouse model system. Compound 18l significantly suppressed weight gain and significantly improved blood parameters such as TG, total cholesterol and NEFA without overt toxic effects.",

keywords = "Anti-obesity, PPAR-γ activator, PTP1B inhibitor, Protein tyrosine phosphatase, Thiazolidinedione",

author = "Bhattarai, {Bharat Raj} and Bhooshan Kafle and Hwang, {Ji Sun} and Ham, {Seung Wook} and Lee, {Keun Hyeung} and Hwangseo Park and Han, {Inn Oc} and Hyeongjin Cho",

note = "Funding Information: Support for this work was provided by Inha University. B. R. Bhattarai and B. Kafle were recipients of a BK21 fellowship. ",

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doi = "10.1016/j.bmcl.2010.08.130",

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T2 - Dual action as PTP1B inhibitors and PPAR-γ activators

AU - Bhattarai, Bharat Raj

AU - Kafle, Bhooshan

AU - Hwang, Ji Sun

AU - Ham, Seung Wook

AU - Lee, Keun Hyeung

AU - Park, Hwangseo

AU - Han, Inn Oc

AU - Cho, Hyeongjin

N1 - Funding Information: Support for this work was provided by Inha University. B. R. Bhattarai and B. Kafle were recipients of a BK21 fellowship.

PY - 2010/11/15

Y1 - 2010/11/15

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AB - Benzylidene-2,4-thiazolidinedione derivatives with substitutions at both the ortho and para-positions of the phenyl group were synthesized as PTP1B inhibitors with IC50 values in a low micromolar range. Compound 18l, the lowest, bore an IC50 of 1.3 μM. In a peroxisome proliferator-activated receptor-γ (PPAR-γ) promoter reporter gene assay, 18l was found to activate the transcription of the reporter gene with potencies comparable to those of troglitazone, rosiglitazone, and pioglitazone. In vivo efficacy of 18l as an anti-obesity and hypoglycemic agent was evaluated in a mouse model system. Compound 18l significantly suppressed weight gain and significantly improved blood parameters such as TG, total cholesterol and NEFA without overt toxic effects.

KW - Anti-obesity

KW - PPAR-γ activator

KW - PTP1B inhibitor

KW - Protein tyrosine phosphatase

KW - Thiazolidinedione

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SN - 0960-894X

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ER -

Novel thiazolidinedione derivatives with anti-obesity effects: Dual action as PTP1B inhibitors and PPAR-γ activators

Abstract

Bibliographical note

Keywords

UN SDGs

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