Human Aldose Reductase Inhibition By (2E)-1-(5-bromothiophen-2-yl)-3- (2-bromophenyl)prop-2-en-1-one – Structure Based Lead Identification By Induced Fit Docking (IFD) Study of the Ligand Crystal Structure Conformation

Solid state structure information for (2E)-1-(5-bromothiophen-2-yl)-3-(2-bromophenyl)prop-2-en-1-one is revealed by using single crystal x-ray diffraction study. The conformation of the molecule in solid state is used to carry out the drug design studies like structure optimization by Density Functional Theory (DFT) and Induced Fit Docking (IFD) study on human aldose reductase. Docking experiments were conducted for the crystal structure conformation inside AR active site using Maestro 9.1v. from Schrödinger Suite 2009. GLIDE scoring function was used to calculate the dock score. The co-crystallized inhibitor (IDD594) in x-ray structure of AR-inhibitor complex (PDB id: 1USO) was taken as reference to correlate the results. In docking study the molecule has shown good binding capacity with a dock score of – 9.49003. The negative score for docking experiment signifies favorable positioning of ligand inside AR active site and the value is comparable to that of reference substrate (– 12.5494). The binding energy in terms of IFD score is estimated to be –694.327 kcal/mol which is close to that of reference (– 697.629 kcal/mol). Results suggested that the molecule can be used as starting point for the development of human aldose reductase inhibitor in fragment based design.