741MOLECULAR DOCKING STUDIES &EVALUATING ANTIDIABETIC ACTIVITY OF THIAZOLIDINEDIONES DERIVATESCurrently available therapies for type 2 diabetes include insulin and various oral agents such as sulfonylureas, metformin, acarbose, and more recently pioglitazone. Each of these agents suffers from generally inadequate efficacy (as monotherapy) and a number of serious adverse effects such as hypoglycemia, GI disturbances and cardiovascular disorders. As a consequence, there continues to be a high demand for new oral antidiabetic drugs devoid of these shortcomings. Novel Thiazolidinediones derivatives was synthesized purified, characterized and subjected to appropriate screening for acute oral toxicity and hypoglycemic activity in Albino mice and Wistar rats respectively. All computational experiments were performed on computer having genuine Intel Pentium Dual Core Processor and Windows XP operating system using the VLifeMDS software package of VLife Technologies Pvt. Ltd. Pune (www.vlifesciences.com). (version 4.3).All the chemicals were of laboratory reagent grade and were obtained from Thomas Baker, Loba Chemi e and Sigma-Aldrich. Melting points were taken in one end sealed glass capillary using Omega melting point apparatus. Analytical thin-layer chromatography was performed on 60F254 Precoated silica gel plates (Merck) to establish identity of reactants and products monitored in between reactions as well at the end for completion of reaction. The spots were visualized in UV chamber or by iodine vapors in an enclosed chamber. Th e solvent system used for Thin-Layer Chromatography was Chloroform: Methanol (5:5) Infra-Red spectra of compounds were recorded using KBr disc method on a shimadzu 1000 FTIR spectrometer in the range of 4000 -200 cm -1 Proton ( 1 H) Nuclear Magnetic Resonance spectra of compounds were recorded on Bruker Avance II 400 NMR Spectrophotometer using DMSO solvent, at SAIF, Punjab University, Chandigarh. Mass spectra of compounds were recorded on DMSO, Q -TOF MICROMASS (LC-MS) at SAIF, Punjab University, Chandigarh. Based on the favorable Antidiabetic activity of thiazolidinedione derivatives, it could be concluded that this hydrophobic interaction played an important effect in the activity. The end a mino cation of PHE287A was also formed a π-cation interaction with the triazole ring of the compound MCR-013-14/15 (distance: 4.56 A 0 ), which enhanced the binding action between receptor PPAR-ᵞ and the ligand compound MCR-013-14/15. The compounds MCR-011 and MCR-014 showed highest percentage decrease of blood glucose level at the dose of 1/10 th that of LD50 among the evaluated compounds compared to control. Acute toxicity study was done for determining LD50. The LD50 was found to be 2000, 1098, 1098,305 mg/Kg for synthesized compounds. Two doses were selected for the hypoglycemic evaluation of the compounds. The compounds MCR-011 and MCR-014 showed highest percentage decrease of blood glucose level at the dose of 1/10 th that of LD50 among the evaluated compounds compared to control. The analysis of structural features revealed that substitution of thiadiazole group enhanced the hypoglycemic potential of the synthesized compounds sushilpharma@rediffmail.comResearch742016Thiadiazole,MCR-011,TriazoleSushil D.Patil,Ashish Kumar SharmaDepartment of Pharmaceutical Chemistry, NIMS Institute of Pharmacy, NIMS University, Shobha Nagar, Delhi Highway Jaipur-303121, Rajasthan, India,Department of Pharmaceutical Chemistry, NIMS Institute of Pharmacy, NIMS University, Shobha Nagar, Delhi Highway Jaipur-303121, Rajasthan, India