%0 Journal Article
%T Molecular Docking and Quantum Mechanical Studies on Pelargonidin-3-Glucoside as Renoprotective ACE Inhibitor
%A Talambedu Usha
%A Pranav Tripathi
%A Veena Pande
%A Sushil Kumar Middha
%J ISRN Computational Biology
%D 2013
%R 10.1155/2013/428378
%X Background and Aim. Despite tangible progress in recent years, substantial therapeutic challenges remain unexplored in nephropathy, particularly in diabetic patient. Addressing these challenges requires identification of novel drugs and development of noninvasive and cost-effective methods to select the most appropriate therapeutic option for the disease. Angiopathic nephropathy is one of the complications of diabetes mellitus and is becoming the single most important reason for end-stage renal disease in the western world. This study has investigated the inhibitory effect of a library naturally occurring nonprotein compounds that inhibit angiotensin converting enzyme (ACE). Materials and Methods. Docking studies of ACE protein with natural compounds and synthetic commercial drug perindopril were done using AutoDock, FlexX, and Hex. Toxicity predictions were carried out using OpenTox. Quantum mechanical properties were studied using GAMESS. Results. Pelargonidin-3-glucoside could be used as a potent renoprotective drug candidate, which inhibits ACEII. It has low toxicity and its quantum mechanical properties are comparable to those of commercial drugs. 1. Introduction Angiotensin converting enzyme (ACE) is an active participant in the body¡¯s renin-angiotensin-aldosterone system for mediation of extracellular volume and arterial vasoconstriction. Secretion of this enzyme is carried by pulmonary and renal endothelial cells to catalyze the conversion of decapeptide angiotensin I to octapeptide angiotensin [1]. Apart from the normal catalysis activity, ACE also degrades bradykinin thus acting as a vasoconstrictor [2]. These two actions make ACE inhibition a potent target in the treatment of conditions such as hypertension, heart failure, and diabetic nephropathy. Inhibition of ACE results in the dwindled formation of angiotensin II and reduced catabolism of bradykinin, leading to systematic dilation of the arteries and veins and a decrease in arterial blood pressure. Inhibition of this enzyme also decreases the risk of end-stage renal disease (ESRD) in diabetics [3]. perindopril is a synthetic chemical drug which inhibits ACE; however, it causes dysfunctioning of the left ventricle of in Duchenne muscular dystrophy [4]. Considering the side effects of perindopril, the present study investigates the inhibitory effect of natural compounds in comparison with perindopril by insilico approach. 2. Materials and Methods To investigate the protein ligand interaction, the natural compounds and perindopril were docked into the active site of ACE predicted by pocket
%U http://www.hindawi.com/journals/isrn.computational.biology/2013/428378/