Indol-1-yl acetic acids as peroxisome proliferator-activated receptor agonists: design, synthesis, structural biology, and molecular docking studies.
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 PPARgamma protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPARgamma protein resulting in potent activity.
Mahindroo
Neeraj
N
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, Republic of China.
Wang
Chiung-Chiu
CC
Liao
Chun-Chen
CC
Huang
Chien-Fu
CF
Lu
I-Lin
IL
Lien
Tzu-Wen
TW
Peng
Yi-Huei
YH
Huang
Wei-Jan
WJ
Lin
Ying-Ting
YT
Hsu
Ming-Chen
MC
Lin
Chia-Hui
CH
Tsai
Chia-Hua
CH
Hsu
John T-A
JT
Chen
Xin
X
Lyu
Ping-Chiang
PC
Chao
Yu-Sheng
YS
Wu
Su-Ying
SY
Hsieh
Hsing-Pang
HP
D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D057927:Hydrophobic and Hydrophilic Interactions; D007210:Indoleacetic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry*; D013329:Structure-Activity Relationship
C509004:2-(5-(3-(6-benzoyl-1-propylnaphthalene-2-yloxy)propoxy)indol-1-yl)ethanoic acid; D007210:Indoleacetic Acids; D008024:Ligands; D009281:Naphthalenes; D047495:PPAR gamma