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.
Mar. Drugs 2014, 12(2), 926-939; https://doi.org/10.3390/md12020926
Received: 24 December 2013
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Revised: 10 January 2014
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Accepted: 22 January 2014
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Published: 13 February 2014
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 3–14. 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.
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Keywords:
PPAR-γ; diabetes; phthalimide; luciferase assay; docking simulation; cell proliferation
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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. https://doi.org/10.3390/md12020926
AMA Style
Xiao B, Su M, Kim EL, Hong J, Chung HY, Kim HS, Yin J, Jung JH. Synthesis of PPAR-γ Activators Inspired by the Marine Natural Product, Paecilocin A. Marine Drugs. 2014; 12(2):926-939. https://doi.org/10.3390/md12020926
Chicago/Turabian StyleXiao, Bin, Mingzhi Su, Eun L. Kim, Jongki Hong, Hae Y. Chung, Hyung S. Kim, Jun Yin, and Jee H. Jung. 2014. "Synthesis of PPAR-γ Activators Inspired by the Marine Natural Product, Paecilocin A" Marine Drugs 12, no. 2: 926-939. https://doi.org/10.3390/md12020926
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