Prachand et al Journal of Drug Delivery & Therapeutics. 2017; 7(7):128-130 ISSN: 2250-1177 [128] CODEN (USA): JDDTAO Available online on 25.12.2017 at http://jddtonline.info Journal of Drug Delivery and Therapeutics Open Access to Pharmaceutical and Medical Research © 2011-17, publisher and licensee JDDT, This is an Open Access article which permits unrestricted non- commercial use, provided the original work is properly cited Open Access Research Article DOCKING STUDIES ON IMIDAZOLIDINE ANALOGUES FOR MANAGEMENT OF DIABETES Sumeet Prachand 1 , Ritu Gilhotra 1 , Arun Gupta 2 , Sanjay Jain 3 , 1 Suresh Gyan Vihar University, Jaipur, India 2 School of Pharmacy, Dr. APJ Abdul Kalam University, Indore, India 3 Indore Institute of Pharmacy, Indore, India E-mail address: sumeet_prachand@gmail.com ABSTRACT Glycogen synthase kinase-3β (GSK-3β) has recently emerged, in the field of medicinal chemistry, as one of the most attractive therapeutic targets for type II diabetes. Phenylmethylene hydantoins (PMHs) forms strong interactions with the hinge region of GSK-3β; carbonyl oxygen at position 2 form a H-bonding with backbone nitrogen of Val135 and the NH at position 3 to the carbonyl oxygen of Asp133. The hydantoin ring was sandwiched between Ala83, on top, and Leu188, on the bottom. The aromatic ring is rotated out of plane from the hydantoin plane, allowing extensive interactions with the nucleotide-binding loop. Furthermore, the substituted benzylidene ring system builds an H-bonding interaction with the guanidine moiety of Arg141. Targeting Arg141 is important to improve the activity in the process of designing new derivatives because it is considered the selectivity residue for GSK-3β. Cite this article as: Prachand S, Gilhotra R, Gupta A, Jain S, Docking studies on imidazolidine analogues for management of diabetes, Journal of Drug Delivery and Therapeutics. 2017; 7(7):128-130 INTRODUCTION: The insulin insensitive form of diabetes, type 2 diabetes mellitus characterized by hyperglycaemia which is also known as elevated blood glucose concentrations, most frequently arises as a consequence of obesity, represents approximately 95% of the overall incidence of diabetes- I. Additionally, diabetes related complications exert a heavy toll on patients with poor metabolic control 1-5 . Most of kinase inhibitors act by competition with either ATP or metal-binding sites that are involved directly in the catalytic process. Over the past 15 years, there have been extensive efforts to understand and reduce the high attrition rates of drug candidates with an increased focus on physicochemical properties. The fruits of this labour have been the generation of numerous efficiency indices, metric-based rules and visualization tools to help guide medicinal chemists in the design of new compounds with more favorable properties. This deluge of information may have had the unintended consequence of further obfuscating molecular optimizations by the inability of these scoring functions, rules and guides to reach a consensus on when a particular transformation is identified as beneficial. In spite of the early discovery of insulin and its subsequent widespread use in the treatment of diabetes mellitus, and later discovery and use of sulfonylureas e.g. chlorpropamide, tolbutamide and biguanides viz. phenformin as oral hypoglycemic agents, the treatment of diabetes mellitus remains less than satisfactory. Insulin can only be administered intravenously due to its chemical nature, and therefore, is troublesome and inconvenient to use. Oral hypoglycemic agents tend to promote side effects such as excessive hypoglycemia or lactic acidosis. Glycogen synthase kinase-3β (GSK-3β) has recently emerged, in the field of medicinal chemistry, as one of the most attractive therapeutic targets for Type II diabetes. The full potential of GSK- 3β inhibitors is yet to be realized and the number of drug candidates being developed by both academic centers and pharmaceutical companies has increased exponentially in the last few years. Glycogen synthase kinase-3β (gsk-3β) is a unique multifunctional serine/threonine kinase that is inactivated by phosphorylation in response to insulin binding; PKB/AKT phosphorylates GSK-3β on serine9, which prevents the enzyme from phosphorylating glycogen synthase. Unphosphorylated glycogen synthase is active & able to synthesize glycogen. Phenylmethylene hydantoins (PMHs) forms strong interactions with the hinge region of GSK-3β; carbonyl oxygen at position 2 form a H-bonding with backbone nitrogen of Val135 and the NH at position 3 to the carbonyl oxygen of Asp133. The hydantoin ring was sandwiched between Ala83, on top, and Leu188, on the bottom. The aromatic ring is rotated out of plane from the hydantoin plane, allowing extensive interactions