Molecular Docking of Flindersine with some targets related to β-cells Protection

Santiagu Stephen Irudayaraj, Antony Stalin, Veeramuthu Duraipandiyan, Savarimuthu Ignacimuthu


Diabetes mellitus (DM) is the most widespread metabolic disorder affecting millions worldwide. Molecular docking studies are useful in identifying some useful ligands which could be used to target proteins related to β-cell protection.  Flindersine isolated from the plant Toddalia asiatica (L.) Lam. (Rutaceae) has been shown by us to possess antidiabetic property. With a view to identify in silico the possible mode of docking with different target proteins like PPARγ and GLUT4 which play important roles in protecting β-cells from damage. Chemical characteristics of Flindersine were retrieved from pubchem database The docking analysis in the active sites of 2PRG and Homology modeled protein structure of GLUT4 were performed by the Auto dock program. The docking results showed good binding interactions of the ligand with both the targets at very low energy level. In our in silico analysis, flindersine isolated from Toddalia asiatica clearly demonstrated that it could improve  diabetic condition by increasing insulin secretion from remnant or regenerated pancreatic beta cells and could promote insulin sensitization and glucose uptake activities. When compared with standard drug Rosiglitazone that is commercially available flindersine can further diminish the degree of shrinkage and necrosis of beta cells of pancreas. Thus flindersine can be considered for developing into a potent antidiabetic drug.

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Duraipandiyan V, Ayyanar M, Ignacimuthu S., Antimicrobial activity of some ethnomedicinal plants used by Paliyar tribe from Tamil Nadu, India, BMC Complement Alt Med, 2006; 6:1-7.

Duraipandiyan V, Ignacimuthu S., Antibacterial and antifungal activity of Flindersine isolated from the traditional medicinal plant, Toddalia asiatica (L.) Lam., J Ethnopharmacol, 2009; 123:494-98.

Karunai Raj M, Balachandran C, Duraipandiyan V, Agastian P, Ignacimuthu S., Antimicrobial activity of Ulopterol isolated from Toddalia asiatica (L.) Lam. A traditional medicinal plant, J Ethnopharmacol 2012; 140:161-165.

Marles RJ, Farnsworth NR., Antidiabetic plants and their active constituents, Phytomedicine, 1995; 2:137-189.

Morris GM., Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ., J Comput Chem, 1998; 19:1639-62.

Muthumani P, Meera R, Devi P, Mohamed SA, Arabath S, Seshu Kumar Koduri, LV, Manavarthi S., Chemical investigation of Toddalia asiatica Lin. and Cardiospermum halicacabum Lin., Int J Drug Form Res, 2010; 1:224-239.

Rajiv Gandhi G, Stalin A, Balakrishna K, Ignacimuthu S, Gabriel Paulraj M, Rajagopal V., Insulin sensitization via partial agonism of PPARγ and glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway by embelin in type 2 diabetic rats, Biochim Biophy Acta, 2013; 1830:2243-55.

Rajkumar M, Chandra RH, Veeresham C., Production of nitidine from callus cultures of Toddalia asiatica, Int J Pharma Sci Nanotechnol, 2010; 3:1028-33.

Sanner MF, Mol. J. 1999. Graph. Model. 17, 57-61.

Singh S, Loke YK, Furberg CD., Thiazolidinediones and heart failure: a teleo-analysis. Diabetes Care, 2007; 8:2148-53.

Stephen Irudayaraj S, Sunil C, Duraipandiyan V, Ignacimuthu S., Antidiabetic and antioxidant activities of Toddalia asiatica (L.) Lam. leaves in Streptozotocin induced diabetic rats, J Ethnopharmacol, 2012; 143:515-23.

Stierand K, Rarey M., Drawing the PDB: Protein−Ligand Complexes in Two Dimensions. Med Chem Lett, 2010; 1(9):540-45.

Tetko IV, Gasteiger J, Todeschini R, Mauri A, Livingstone D, Ertl P, Palyulin VA, Radchenko EV, Zefirov NS, Makarenko AS, Tanchuk VY, Prokopenko VV., Comput J Aid Mol Des, 2005; 19: 453-63.

Wang F, Xub Y, Liua J., New geranyloxycoumarins from Toddalia asiatica, J Asian Nat Prod Res, 2009; 11:752-56.

Wild SG, Roglic A, Green R, Sicree R, King H., Global prevalence of diabetes: estimated for the year 2000 and projection for 2030. Diabetes Care, 2004; 5:1047-53.