Next Article in Journal
Antimicrobial Activity of the Marine Alkaloids, Clathrodin and Oroidin, and Their Synthetic Analogues
Previous Article in Journal
Bioprospecting from Marine Sediments of New Brunswick, Canada: Exploring the Relationship between Total Bacterial Diversity and Actinobacteria Diversity
Article Menu

Export Article

Open AccessArticle
Mar. Drugs 2014, 12(2), 926-939; https://doi.org/10.3390/md12020926

Synthesis of PPAR-γ Activators Inspired by the Marine Natural Product, Paecilocin A

1
College of Pharmacy, Pusan National University, Busan 609-735, Korea
2
College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
3
College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea
4
College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea
*
Author to whom correspondence should be addressed.
Received: 24 December 2013 / Revised: 10 January 2014 / Accepted: 22 January 2014 / Published: 13 February 2014
View Full-Text   |   Download PDF [927 KB, uploaded 24 February 2015]   |  

Abstract

A series of N-substituted phthalimide derivatives were synthesized based on a pharmacophore study of paecilocin A (a natural PPAR-γ agonist) and synthetic leads. The introduction of hydrophilic and hydrophobic groups to the phthalimide skeleton yielded compounds 314. Compound 7 showed significant PPAR-γ activation in a luciferase assay using rat liver Ac2F cells. Docking simulations showed that a free hydroxyl group on the phthalimide head and a suitable hydrophilic tail, including a phenyl linker, were beneficial for PPAR-γ activation. Compound 7 and rosiglitazone concentration-dependently activated PPAR-γ with EC50 values of 0.67 μM and 0.028 μM, respectively. These phthalimide derivatives could be further investigated as a new class of PPAR-γ ligands. View Full-Text
Keywords: PPAR-γ; diabetes; phthalimide; luciferase assay; docking simulation; cell proliferation PPAR-γ; diabetes; phthalimide; luciferase assay; docking simulation; cell proliferation
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Xiao, B.; Su, M.; Kim, E.L.; Hong, J.; Chung, H.Y.; Kim, H.S.; Yin, J.; Jung, J.H. Synthesis of PPAR-γ Activators Inspired by the Marine Natural Product, Paecilocin A. Mar. Drugs 2014, 12, 926-939.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top