Isolation, Characterization and Structure Elucidation of Antidiabetic Compound “2-({4-oxo-1H,2H,3H,4H,4aH-cyclopenta[b]pyridine-2-yl} methyl)-1H, 2H, 3H, 4H, 4aH-Cyclopenta[b]Pyridine-4-one” from the barks of Parkia timoriana (DC.) Merr.

Abstract

Parkia timoriana (D.C.) Merr is a medicinal plant with long-known usage as a traditional medicine. This plant’s bark and pods have been used in medicine and food supplements. P. timoriana bark was extracted with ethyl acetate and purified using silica gel column chromatography. A pure compound, 2-({4-oxo-1H, 2H, 3H, 4H, 4aH-cyclopenta[b]pyridine-2-yl}methyl)-1H, 2H, 3H, 4H, 4Ah cyclopenta[b]pyridine-4-one (BCPP) was isolated and spectroscopic analysis was performed to determine its chemical structure. Antidiabetic studies were conducted using Bis-Cyclopenta-Pyridin (BCPP) for its enzymatic inhibition. In vitro cell culture assays, gene expression studies and in silico docking studies were done to ascertain the antidiabetic activity. P. timoriana bark was extracted using the solvents based on its polarity: hexane, ethyl acetate and methanol. At a 125 μg/ml concentration, BCPP demonstrated 75% inhibition of alpha-amylase, 74% inhibition of alpha-glucosidase and a 59% increase in glucose uptake by yeast cells (3.3 ± 0.0058 at 125 μg/ml). BCPP increased the expression of the PPARγ gene in 3T3-L1 cells by 0.23-fold. There is an increase in fold change of PPAR- γ at 25 μg/ml – 0.11-fold; at 50 μg /ml – 0.25-fold; at 75 μg /ml – 0.37-fold; 100 μg /ml – 0.73-fold; and at 125 μg/ml, there is an upregulation of 1.10-fold in 3T3-L1 cells. In silico docking studies confirmed the alpha-amylase and alpha-glucosidase inhibitory activities of BCPP. This study suggests the application of BCPP as a potential antidiabetic agent that can be used in drug design and pharmaceutics.