Abstract

STRUCTURE BASED DRUG DESIGN SYNTHESIS AND CHARACTERIZATION OF SOME NOVEL PHOSPHODIESTERASE 5 INHIBITOR

*Payal Agrawal, Priyanka Chaturvedi and Surendra Jain

Abstract

In the present work, we designed and synthesized novel 6-oxo-4- substitute aryl-2-sulfanyl- 1, 3-dihydropyrimidine-5 carbonitriles derivatives with preferential-selective PDE- 5 inhibition activity and docking scores binding activity. 2,50,000 molecules from OTAVA database was screened against phosphodiesterase 5 crystal structure (PDB ID: 1UHO) by high-throughput virtual screening using flexible docking in order to improve the precision of docking performance by optimizing functional group binding interactions to the active site residues. After evaluation the 6-oxo-4-(3-nitrobenzaldehyde)-2- sulfanyl-1,3-dihydropyridine- 5-carbonitriles compound (PA 15-07) showed good docking score binding activity with docking score (-5.36 and preferential selective for PDE 5. In addition we found that compound PA 15-07 with molecular weight (C11H6N4O3S) and molecular formula (274) is crystalline in nature in orange colour. We also found that this compound is soluble in (chloroform, water, ethanol, methanol and DMSO) with highest Rf value (0.94) and % yield (92.64). Molecular docking attributed its good activity to its key binding interactions in PDE-5 active site with additional hydrogen bonding with amino acids lining the metal pocket.

Keywords: Phosphodiesterase 5, Current Good Manufacturing Practice, OTAVA, High Throughput Virtual Screening, Molecular Docking.