Computational evaluation of Isoorientin (C-glycosyl flavone) on PPAR-gamma receptors and HMG-CoA reductase using MOE 2008.10

Peroxisome proliferators-activated receptor-gamma (PPAR-gamma) plays an essential role in lipid and glucose homeostasis. Numerous studies and comprehensive reviews have documented various naturally derived ligands as PPAR-γ a potential source of novel anti-diabetic compounds from plants and herbs [1]. Isoorientin, a C-glycosyl flavone, has been isolated as an antidiabetic and antihyperlipidemic agent from aerial parts of Gentiana ollivieri Griseb. [2]. The objective of this study is to find out, the relation between these receptors and ligand. We used docking property and site finder and electrostatic map tools of molecular operating environment (MOE) 2008.10 computer programme from Chemical computing group. Protein structures were taken from Protein Data Bank PDB and operated with Protonate 3D and minimized. Ligands were designed by LigX.

Results shown that, E score1: -16.0501 and E refine: -32.3072 for isoorientin-PPAR gamma docking study, E score1: -9.8957 and E refine: -17.2581 for isoorientin-HMG-CoA docking study. Data obtained from experiments demonstrated that isoorientin can be candidate as a good multi-target drug template.

Acknowledgements: Authors to thank Ms. Patricia Middleton from Chemical Computing Group INC. for supply MOE 2008.10 programme.

References: [1] Salam, N.K. et al. (2008) Chem. Biol. Drug Des. 71:57–70.

[2] Sezik, E. et al. (2005) Life Sci. 76:1223–1238.

[3] Labute, P. et al. (2008) Electrostatic Maps, Chemical Computing Group, Montreal, Canada.