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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| Format: | Article |
| Language: | English |
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MDPI AG
2016-06-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/14/6/112 |
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| author | So Hyeon Eom Sen Liu Mingzhi Su Tae Hwan Noh Jongki Hong Nam Deuk Kim Hae Young Chung Min Hye Yang Jee H. Jung |
| author_facet | So Hyeon Eom Sen Liu Mingzhi Su Tae Hwan Noh Jongki Hong Nam Deuk Kim Hae Young Chung Min Hye Yang Jee H. Jung |
| author_sort | So Hyeon Eom |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T08:10:58Z |
| format | Article |
| id | doaj.art-22074e6ddade466ebe8497380bdbdc0d |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-12-10T08:10:58Z |
| publishDate | 2016-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-22074e6ddade466ebe8497380bdbdc0d2022-12-22T01:56:34ZengMDPI AGMarine Drugs1660-33972016-06-0114611210.3390/md14060112md14060112Synthesis of Phthalimide Derivatives as Potential PPAR-γ LigandsSo Hyeon Eom0Sen Liu1Mingzhi Su2Tae Hwan Noh3Jongki Hong4Nam Deuk Kim5Hae Young Chung6Min Hye Yang7Jee H. Jung8College of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Kyung Hee University, Seoul 02447, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaPaecilocin 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.http://www.mdpi.com/1660-3397/14/6/112PPAR-γ agonistpaecilocin Atype 2 diabetesphthalimideadipogenesis3T3-L1 |
| spellingShingle | So Hyeon Eom Sen Liu Mingzhi Su Tae Hwan Noh Jongki Hong Nam Deuk Kim Hae Young Chung Min Hye Yang Jee H. Jung Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands Marine Drugs PPAR-γ agonist paecilocin A type 2 diabetes phthalimide adipogenesis 3T3-L1 |
| title | 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_short | Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands |
| title_sort | synthesis of phthalimide derivatives as potential ppar γ ligands |
| topic | PPAR-γ agonist paecilocin A type 2 diabetes phthalimide adipogenesis 3T3-L1 |
| url | http://www.mdpi.com/1660-3397/14/6/112 |
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