Pharmacophore-driven identification of PPAR¿ agonists from natural sources
Research output: Contribution to journal › Journal article › Research › peer-review
In a search for more effective and safe anti-diabetic compounds, we developed a pharmacophore model based on partial agonists of PPAR¿. 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 PPAR¿ agonist through bioassay-guided chromatographic fractionations of Chios mastic gum fractions, whereas some other sub-fractions exhibited also biological activity towards PPAR¿. 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 PPAR¿ 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 |
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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 - 2011 |
- Animals, Cell Line, Dose-Response Relationship, Drug, Drug Discovery, Fibroblasts, Hypoglycemic Agents, Mice, PPAR gamma, Pistacia, Plant Extracts, Triterpenes
Research areas
ID: 35409822