Discovery and development of statins different pharmacophore structure were found. This structure-based virtual screening procedure is considered promising for rational quest and optimization of potential novel HGMR inhibitors. Discovery and development of statins The discovery of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors, called statins, was a breakthrough in the prevention of hypercholesterolemia and related diseases. Hypercholesterolemia is considered to be one of the major risk factors for atherosclerosis which often leads to cardiovascular, cerebrovascular and peripheral vascular diseases. The statins inhibit cholesterol synthesis in the body and that leads to reduction in blood cholesterol levels, which is thought to reduce the risk of atherosclerosis and diseases caused
Discovery and development of statins that the statins exploit and is used to accommodate their hydrophobic moieties. The specificity and the tight binding of statins is due to orientation and bonding interactions that form between the statin and the HMGR enzyme. Polar interactions are formed between the HMG-moiety and residues that are located in the cis loop of the enzyme. These polar interactions are between Ser, Asp, Lys and Lys (Figure 4). The terminal carboxylate of the HMG moiety forms a salt bridge with the cationic Lys of the enzyme. In addition to the polar interaction, Lys participates in a hydrogen bonding network with Glu,