Shweta Mishra1*, Rashmi Dahima2
1Sri Aurobindo Institute of Pharmacy, Ujjain Highway,Gram Bhavarasla, Indore, Madhya Pradesh 453111, India
2School of Pharmacy, Devi Ahilya Vishwavidyalaya, Takshila Parisar, Indore, Madhya Pradesh 452020, India
*Address for Corresponding Author
Sri Aurobindo Institute of Pharmacy, Ujjain Highway,Gram Bhavarasla, Indore, Madhya Pradesh 453111 India
Background: Diabetes mellitus is increasing globally affecting more than 180 million people worldwide. Thiazolidinediones (TZDs), Metformin, Sulfonylureas (SURs) are well-known drugs however, side-effects are associated with it which limits its use. Adiponectin Receptor 1 (AdipoR1) has been recently identified as an attractive anti-diabetic target as it plays a crucial role in regulating hyperlipidemic conditions which lead to obesity and increasing glucose transfer, gluconeogenesis and insulin sensitivity in pancreatic β-cells for the treatment of type 2 diabetes mellitus (T2DM). Objective: objective of present work was to design a drug molecule which can target adiponectin and Peroxisome proliferator-activated receptor as a target for treatment of diabetes mellitus. Material and methods: In this work, designing strategy relied on making a structural similarity having Peroxisome proliferator-activated receptor and Adiponectin Receptor 1 modulating activity. In this study to further investigate, the compounds were docked with individual receptor active sites, to study the stability of their complexes with both proteins and final binding orientations of these molecules. After the absorption, distribution, metabolism and excretion properties of the derivatives possessing a good binding affinity for all the receptors were evaluated. Later on, the in-silico toxicity studies were also performed. Results and conclusion: The positive results of these compounds showed that they can be further studied for the in-vitro and in-vivo activities after synthesis. Thus, these derivatives might be promising lead compounds for the treatment of diabetes mellitus without the allied risk of hypoglycemia and cardiovascular risks.
Keywords: PPAR-G, AdipoR1, virtual screening, structural similarity, docking, Type 2 diabetes mellitus