Indol-1-yl acetic acids as peroxisome proliferator-activated receptor agonists

Design, synthesis, structural biology, and molecular docking studies

Neeraj Mahindroo, Chiung Chiu Wang, Chun Chen Liao, Chien Fu Huang, I. Lin Lu, Tzu Wen Lien, Yi Huei Peng, Wei Jan Huang, Ying Ting Lin, Ming Chen Hsu, Chia Hui Lin, Chia Hua Tsai, John T A Hsu, Xin Chen, Ping Chiang Lyu, Yu Sheng Chao, Su Ying Wu, Hsing Pang Hsieh

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

A series of novel indole-based PPAR agonists is described leading to discovery of 10k, a highly potent PPAR pan-agonist. The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPARγ protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPARγ protein resulting in potent activity.

Original languageEnglish
Pages (from-to)1212-1216
Number of pages5
JournalJournal of Medicinal Chemistry
Volume49
Issue number3
DOIs
Publication statusPublished - Feb 9 2006
Externally publishedYes

Fingerprint

Peroxisome Proliferator-Activated Receptors
Molecular Biology
Acetates
Hydrophobic and Hydrophilic Interactions
Proteins
Ligands

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Indol-1-yl acetic acids as peroxisome proliferator-activated receptor agonists : Design, synthesis, structural biology, and molecular docking studies. / Mahindroo, Neeraj; Wang, Chiung Chiu; Liao, Chun Chen; Huang, Chien Fu; Lu, I. Lin; Lien, Tzu Wen; Peng, Yi Huei; Huang, Wei Jan; Lin, Ying Ting; Hsu, Ming Chen; Lin, Chia Hui; Tsai, Chia Hua; Hsu, John T A; Chen, Xin; Lyu, Ping Chiang; Chao, Yu Sheng; Wu, Su Ying; Hsieh, Hsing Pang.

In: Journal of Medicinal Chemistry, Vol. 49, No. 3, 09.02.2006, p. 1212-1216.

Research output: Contribution to journalArticle

Mahindroo, N, Wang, CC, Liao, CC, Huang, CF, Lu, IL, Lien, TW, Peng, YH, Huang, WJ, Lin, YT, Hsu, MC, Lin, CH, Tsai, CH, Hsu, JTA, Chen, X, Lyu, PC, Chao, YS, Wu, SY & Hsieh, HP 2006, 'Indol-1-yl acetic acids as peroxisome proliferator-activated receptor agonists: Design, synthesis, structural biology, and molecular docking studies', Journal of Medicinal Chemistry, vol. 49, no. 3, pp. 1212-1216. https://doi.org/10.1021/jm0510373
Mahindroo, Neeraj ; Wang, Chiung Chiu ; Liao, Chun Chen ; Huang, Chien Fu ; Lu, I. Lin ; Lien, Tzu Wen ; Peng, Yi Huei ; Huang, Wei Jan ; Lin, Ying Ting ; Hsu, Ming Chen ; Lin, Chia Hui ; Tsai, Chia Hua ; Hsu, John T A ; Chen, Xin ; Lyu, Ping Chiang ; Chao, Yu Sheng ; Wu, Su Ying ; Hsieh, Hsing Pang. / Indol-1-yl acetic acids as peroxisome proliferator-activated receptor agonists : Design, synthesis, structural biology, and molecular docking studies. In: Journal of Medicinal Chemistry. 2006 ; Vol. 49, No. 3. pp. 1212-1216.
@article{df68b3f1616d4db08fb484c92a70c416,
title = "Indol-1-yl acetic acids as peroxisome proliferator-activated receptor agonists: Design, synthesis, structural biology, and molecular docking studies",
abstract = "A series of novel indole-based PPAR agonists is described leading to discovery of 10k, a highly potent PPAR pan-agonist. The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPARγ protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPARγ protein resulting in potent activity.",
author = "Neeraj Mahindroo and Wang, {Chiung Chiu} and Liao, {Chun Chen} and Huang, {Chien Fu} and Lu, {I. Lin} and Lien, {Tzu Wen} and Peng, {Yi Huei} and Huang, {Wei Jan} and Lin, {Ying Ting} and Hsu, {Ming Chen} and Lin, {Chia Hui} and Tsai, {Chia Hua} and Hsu, {John T A} and Xin Chen and Lyu, {Ping Chiang} and Chao, {Yu Sheng} and Wu, {Su Ying} and Hsieh, {Hsing Pang}",
year = "2006",
month = "2",
day = "9",
doi = "10.1021/jm0510373",
language = "English",
volume = "49",
pages = "1212--1216",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "3",

}

TY - JOUR

T1 - Indol-1-yl acetic acids as peroxisome proliferator-activated receptor agonists

T2 - Design, synthesis, structural biology, and molecular docking studies

AU - Mahindroo, Neeraj

AU - Wang, Chiung Chiu

AU - Liao, Chun Chen

AU - Huang, Chien Fu

AU - Lu, I. Lin

AU - Lien, Tzu Wen

AU - Peng, Yi Huei

AU - Huang, Wei Jan

AU - Lin, Ying Ting

AU - Hsu, Ming Chen

AU - Lin, Chia Hui

AU - Tsai, Chia Hua

AU - Hsu, John T A

AU - Chen, Xin

AU - Lyu, Ping Chiang

AU - Chao, Yu Sheng

AU - Wu, Su Ying

AU - Hsieh, Hsing Pang

PY - 2006/2/9

Y1 - 2006/2/9

N2 - A series of novel indole-based PPAR agonists is described leading to discovery of 10k, a highly potent PPAR pan-agonist. The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPARγ protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPARγ protein resulting in potent activity.

AB - A series of novel indole-based PPAR agonists is described leading to discovery of 10k, a highly potent PPAR pan-agonist. The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPARγ protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPARγ protein resulting in potent activity.

UR - http://www.scopus.com/inward/record.url?scp=32344437952&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=32344437952&partnerID=8YFLogxK

U2 - 10.1021/jm0510373

DO - 10.1021/jm0510373

M3 - Article

VL - 49

SP - 1212

EP - 1216

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 3

ER -