| Publication Type |
Journal Article |
| Title |
Design, synthesis and biological evaluation of a class of bioisosteric oximes of the novel dual peroxisome proliferator-activated receptor alpha/gamma ligand LT175 |
| Authors |
Luca Piemontese Giuseppe Fracchiolla Antonio Carrieri Mariagiovanna Parente Antonio Laghezza Giuseppe Carbonara Sabina Sblano Marilena Tauro Federica Gilardi Paolo Tortorella Antonio Lavecchia Maurizio Crestani Beatrice Desvergne Fulvio Loiodice |
| Groups |
|
| Journal |
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY |
| Year |
2015 |
| Month |
January |
| Volume |
90 |
| Number |
|
| Pages |
583-594 |
| Abstract |
The effects resulting from the introduction of an oxime group in place of the distal aromatic ring of the diphenyl moiety of LT175, previously reported as a PPAR alpha/gamma dual agonist, have been investigated. This modification allowed the identification of new bioisosteric ligands with fairly good activity on PPAR alpha and fine-tuned moderate activity on PPAR gamma. For the most interesting compound (S)-3, docking studies in PPAR alpha and PPAR gamma provided a molecular explanation for its different behavior as full and partial agonist of the two receptor isotypes, respectively. A further investigation of this compound was carried out performing gene expression studies on HepaRG cells. The results obtained allowed to hypothesize a possible mechanism through which this ligand could be useful in the treatment of metabolic disorders. The higher induction of the expression of some genes, compared to selective agonists, seems to confirm the importance of a dual PPAR alpha/gamma activity which probably involves a synergistic effect on both receptor subtypes. (C) 2014 Elsevier Masson SAS. All rights reserved. |
| DOI |
http://dx.doi.org/10.1016/j.ejmech.2014.11.044 |
| ISBN |
|
| Publisher |
|
| Book Title |
|
| ISSN |
0223-5234 |
| EISSN |
1768-3254 |
| Conference Name |
|
| Bibtex ID |
ISI:000348951900048 |
| Observations |
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