Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands

Paecilocin A, a phthalide derivative isolated from the jellyfish-derived fungus Paecilomyces variotii, activates PPAR-γ (Peroxisome proliferator-activated receptor gamma) in rat liver Ac2F cells. Based on a SAR (Structure-activity relationships) study and in silico analysis of paecilocin A-mimetic d...

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Main Authors:	Eom, So Hyeon, Liu, Sen, Su, Mingzhi, Noh, Tae Hwan, Hong, Jongki, Kim, Nam Deuk, Chung, Hae Young, Yang, Min Hye, Jung, Jee H.
Format:	Online
Language:	English
Published:	MDPI 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926071/

id	pubmed-4926071
recordtype	oai_dc
spelling	pubmed-49260712016-07-06 Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands Eom, So Hyeon Liu, Sen Su, Mingzhi Noh, Tae Hwan Hong, Jongki Kim, Nam Deuk Chung, Hae Young Yang, Min Hye Jung, Jee H. Communication Paecilocin A, a phthalide derivative isolated from the jellyfish-derived fungus Paecilomyces variotii, activates PPAR-γ (Peroxisome proliferator-activated receptor gamma) in rat liver Ac2F cells. Based on a SAR (Structure-activity relationships) study and in silico analysis of paecilocin A-mimetic derivatives, additional N-substituted phthalimide derivatives were synthesized and evaluated for PPAR-γ agonistic activity in both murine liver Ac2F cells and in human liver HepG2 cells by luciferase assay, and for adipogenic activity in 3T3-L1 cells. Docking simulation indicated PD6 was likely to bind most strongly to the ligand binding domain of PPAR-γ by establishing crucial H-bonds with key amino acid residues. However, in in vitro assays, PD1 and PD2 consistently displayed significant PPAR-γ activation in Ac2F and HepG2 cells, and adipogenic activity in 3T3-L1 preadipocytes. MDPI 2016-06-08 /pmc/articles/PMC4926071/ /pubmed/27338418 http://dx.doi.org/10.3390/md14060112 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Eom, So Hyeon Liu, Sen Su, Mingzhi Noh, Tae Hwan Hong, Jongki Kim, Nam Deuk Chung, Hae Young Yang, Min Hye Jung, Jee H.
spellingShingle	Eom, So Hyeon Liu, Sen Su, Mingzhi Noh, Tae Hwan Hong, Jongki Kim, Nam Deuk Chung, Hae Young Yang, Min Hye Jung, Jee H. Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands
author_facet	Eom, So Hyeon Liu, Sen Su, Mingzhi Noh, Tae Hwan Hong, Jongki Kim, Nam Deuk Chung, Hae Young Yang, Min Hye Jung, Jee H.
author_sort	Eom, So Hyeon
title	Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands
title_short	Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands
title_full	Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands
title_fullStr	Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands
title_full_unstemmed	Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands
title_sort	synthesis of phthalimide derivatives as potential ppar-γ ligands
description	Paecilocin A, a phthalide derivative isolated from the jellyfish-derived fungus Paecilomyces variotii, activates PPAR-γ (Peroxisome proliferator-activated receptor gamma) in rat liver Ac2F cells. Based on a SAR (Structure-activity relationships) study and in silico analysis of paecilocin A-mimetic derivatives, additional N-substituted phthalimide derivatives were synthesized and evaluated for PPAR-γ agonistic activity in both murine liver Ac2F cells and in human liver HepG2 cells by luciferase assay, and for adipogenic activity in 3T3-L1 cells. Docking simulation indicated PD6 was likely to bind most strongly to the ligand binding domain of PPAR-γ by establishing crucial H-bonds with key amino acid residues. However, in in vitro assays, PD1 and PD2 consistently displayed significant PPAR-γ activation in Ac2F and HepG2 cells, and adipogenic activity in 3T3-L1 preadipocytes.
publisher	MDPI
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926071/
_version_	1613601261440991232

Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands

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