Molecular docking studies of 4 - Piperidinopyridine and 4 - Piperidinopyrimidine derivatives as 2,3 - Oxidosqualene Cyclase inhibitors
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Date
2011
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Abstract
Lanosterol synthase belongs to the large family of oxidosqualene cyclases (OSCs), eukaryotic enzymes that catalyse the
cyclization of 2,3-oxidosqualene(OS) into different cyclic compounds. A novel series of 4-piperidinopyridines and 4-
piperidinopyrimidines showed potent and selective inhibition of 2,3-oxidosqualenc cyclase-lanosterol synthase (OSC). The
piperidinopyrimidine OSC inhibitors have a significantly lower pl<.(a) than the corresponding pyridine .This indicates that
other novel OSC inhibitors may be found in analogues of this series across a broader pl<.(a) range (6.0-9.0). These series may
yield novel hypccholesterolemic agents for the treatment of cardiovascular disease. Docking analysis of GOLD and GLIDE
were performed to predict the binding properties of disease related targef protein OSC with 4-Piperidinopyridine and 4-
Piperidinopyrimidine derivatives as inhibitors. Virtual Screening has been done for all derivatives (inhibitors) and the ligands
were chosen for induced fit docking based on their binding affinity, glide energy and glide score. The results revealed that the
compound 25 (I-(4-Pyrimiclinyl)-4-(I-(4-brninopl]unyl -siilfonyl)piperazin-4ylcarbonyl)piperidine) with more interaction
and scores may afford novel hypocholcstorolemic agents for the treatment of cardiovascular disease.