Mar. Drugs 2014, 12(2), 926-939; doi:10.3390/md12020926
Article

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

1,2email, 1email, 1email, 3email, 1email, 4email, 2email and 1,* email
Received: 24 December 2013; in revised form: 10 January 2014 / Accepted: 22 January 2014 / Published: 13 February 2014
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
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.

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.

Chicago/Turabian Style

Xiao, Bin; Su, Mingzhi; Kim, Eun L.; Hong, Jongki; Chung, Hae Y.; Kim, Hyung S.; Yin, Jun; Jung, Jee H. 2014. "Synthesis of PPAR-γ Activators Inspired by the Marine Natural Product, Paecilocin A." Mar. Drugs 12, no. 2: 926-939.

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