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.
Bibliographical noteThe online version of this article (doi:10.1007/s10822-010-9398-5) contains supplementary material, which is available to authorized users.
- PPARc agonist
- Pharmacophore model
- Virtual screening
- Natural compounds
Petersen, R. K., Christensen, K. B., Assimopoulou, A. N., Fretté, X., Papageorgiou, V. P., Kristiansen, K., & Kouskoumvekaki, I. (2011). Pharmacophore-driven identification of PPARγ agonists from natural sources. Journal of Computer - Aided Molecular Design, 25(2), 107-116. https://doi.org/10.1007/s10822-010-9398-5