Computational and molecular designing studies of novel flavonoid analogues as HMG CoA Reductase and cholesterol esterase inhibitors for their Cardioprotective effect using in Silico docking studies
Journal Title: International Journal of Research in Pharmacology & Pharmacotherapeutics (IJRPP) - Year 2018, Vol 7, Issue 2
Abstract
The objective of the study was to generate a series of pharmacophores from a parent flavone skeleton and evaluate their in silico HMG CoA reductase and cholesterol esterase enzyme inhibitory potential using the software AutoDock 4.2. A total of eighteen flavonoid compounds were generated from flavone structure using the software ChemSketch. The docking studies were carried out for all these compounds using the software AutoDock4.2 with the enzymes HMG CoA reductase and cholesterol esterase. The docking parameters like binding energy, inhibition constant and intermolecular energy were determined. The results obtained were compared with the standard drugs. Rosuvastatin and simvastatin were used as the standards for HMG CoA reductase and cholesterol esterase inhibitory activity respectively. The binding sites of both enzymes for these ligands and their pharmacophores were identified. Based on the docking parameters for the enzyme HMG CoA reductase the binding energy, inhibition constant, intermolecular energy of Rosuvastatin was found to be -7.97 kcalmol-1 , 1.44nm was and -11.85 kcalmol-1 respectively. The flavonoid compounds showed binding energy ranging between -11.85 to -9.09 to kcalmol-1 , inhibition constant ranging from 2.06 nM to 216.45 nM intermolecular energy ranging between -13.94 kcalmol-1 to - 10.88 kcalmol-1 . Among the flavonoid compounds FA5 showed better binding energy -11.85 kcalmol-1 , inhibition constant (2.06 nM) and intermolecular energy (-13.94 kcalmol-1 ) when compared to the standard.The docking parameters of standard Simvastatin to cholesterol esterase exhibited a binding energy -6.72 kcalmol-1 , inhibition constant (11.89 nm) and intermolecular energy -9.11 kcalmol-1 . The flavonoid compounds showed binding energy ranging between -9.03 kcalmol-1 to -7.28 kcalmol-1 , inhibition constant ranging from 241.43 nm to 4.71 μM, intermolecular energy ranging between -10.69 kcalmol-1 to -9.37 kcalmol-1 . From the selected flavonoids FA12 had showed better binding energy (-9.03 kcal/mol), inhibition constant (241.43 nm), when compared to the standard simvastatin (-6.72 kcalmol-1 ). This proved that FA12 has the potential to inhibit cholesterol esterase. The compound FA2 exhibited better intermolecular energy -10.69 kcalmol1 ) when compared to the standard and the compound FA12. In conclusion, these results indicate that selected flavonoids, FA5 has better binding sites and interaction for the enzyme HMG CoA reductase and FA12 have better binding sites and interactions with cholesterol esterase enzyme and can be synthesized and screened for their in vitro and in vivo potential.
Authors and Affiliations
K. Asok Kumar
Keywords
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