TY - JOUR
T1 - Pharmacophore-driven identification of PPAR¿ agonists from natural sources
AU - Petersen, Rasmus Koefoed
AU - Christensen, Kathrine Bisgaard
AU - Assimopoulou, Andreana N
AU - Fretté, Xavier
AU - Papageorgiou, Vassilios P
AU - Kristiansen, Karsten
AU - Kouskoumvekaki, Irene
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Line
KW - Dose-Response Relationship, Drug
KW - Drug Discovery
KW - Fibroblasts
KW - Hypoglycemic Agents
KW - Mice
KW - PPAR gamma
KW - Pistacia
KW - Plant Extracts
KW - Triterpenes
U2 - 10.1007/s10822-010-9398-5
DO - 10.1007/s10822-010-9398-5
M3 - Journal article
C2 - 21069556
SN - 0920-654X
VL - 25
SP - 107
EP - 116
JO - Journal of Computer-Aided Molecular Design
JF - Journal of Computer-Aided Molecular Design
IS - 2
ER -
