INSILCO MOLECULAR DOCKING STUDY OF DIHYDROISOQUINOLINIUM DERIVATIVES AS DPP IV INHIBITORS IN TYPE II DIABETES MELLITUS
{ DOWNLOAD AS PDF }
ABOUT AUTHORS
Amiya Kumar Ghosh*1, Shiladitya Palit2, SaptarshiSamajdar3
1Dept. of Pharmacy, Utkal University, Orissa
2Dept. of Pharmacy, IITBHU
3Centre for Pharmaceutical Sc. And Natural Products, Central University of Punjab
amiyaghosh94@gmail.com
ABSTRACT:
With the spread of western lifestyles, the occurrence of diabetes in the world’s population is rising. Diabetes is a complex metabolic endocrine disorder that occurs when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. It is classified into two basic forms Type I and Type II diabetes. A major goal for the treatment of type II diabetes is the enhancement of insulin secretion by pancreatic islet b-cells. The current therapeutic agents, although effective in increasing insulin secretion, are associated with undesirable side effects. Dipeptidyl peptidase IV (DPP IV) is responsible for conversion of glucose tolerance (GLP-1), into inactive form. The inhibition of DPP-IV would be beneficial in the treatment of diabetes mellitus. Improved glucose tolerance in diabetic patients was achieved with several small molecules as DPP IV inhibitors, including sitagliptin. The current study was designed to identify a suitable inhibitor agent for DPP IV. Computer-assisted molecular modeling approach has contributed to the successful discovery of several novel antidiabetic DPP IV agents.Someisoquinoline was designed computationally and screened through insilico docking studies against crystal structure of Dipeptidylpeptidase-IV (DPP-IV) ( PDB entry 2P8S )as a projected target for Type 2 Diabetes Mellitus.Insilico docking methodology using Auto Dock vina comprising a search method Genetic Lamarckian algorithm was used. Genetic Lamarckian algorithm performs an Automated Docking and has an advantage of empirical binding free energy force field that allows the prediction of binding free energies for docked ligands. In-silico evaluation shows satisfactory docking results, when compared with standard using docking. It is concluded that investigational ligands has the potential of inhibiting DPP-IV and there by further screening (invitro and invivo) studies can be carried out in order to find out optimized bioflavonoids for treating type2diabetes mellitus.
.png)
