Abstract
In a search for more effective and safe anti-diabetic compounds, we developed a pharmacophore model based on partial agonists of PPARγ. The model was used for the virtual screening of the Chinese Natural Product Database (CNPD), a library of plant-derived natural products primarily used in folk medicine. From the resulting hits, we selected methyl oleanonate, a compound found, among others, in Pistacia lentiscus var. Chia oleoresin (Chios mastic gum). The acid of methyl oleanonate, oleanonic acid, was identified as a PPARγ agonist through bioassay-guided chromatographic fractionations of Chios mastic gum fractions, whereas some other sub-fractions exhibited also biological activity towards PPARγ. The results from the present work are two-fold: on the one hand we demonstrate that the pharmacophore model we developed is able to select novel ligand scaffolds that act as PPARγ agonists; while at the same time it manifests that natural products are highly relevant for use in virtual screening-based drug discovery.
| Original language | English |
|---|---|
| Journal | Journal of Computer - Aided Molecular Design |
| Volume | 25 |
| Issue number | 2 |
| Pages (from-to) | 107-16 |
| Number of pages | 10 |
| ISSN | 0920-654X |
| DOIs | |
| Publication status | Published - Feb 2011 |
Keywords
- Animals
- Cell Line
- Dose-Response Relationship, Drug
- Drug Discovery
- Fibroblasts
- Hypoglycemic Agents
- Mice
- PPAR gamma
- Pistacia
- Plant Extracts
- Triterpenes
