Abstract
Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease (AD) are the two disorders which are known to share pertinent pathological and therapeutic links. Sodium glucose co-transporter-2 (SGLT2) and Acetylcholinesterase (AChE) are established inhibition targets for T2DM and AD treatments, respectively. Reports suggest that anti-diabetic drugs could be used for AD treatment also. The present study used molecular docking by Autodock4.2 using our Click-By-Click-protocol, Ligplot1.4.3 and change in accessible surface area (ASA)-calculations to investigate the binding of two investigational anti-diabetic drugs, Ertugliflozin and Sotagliflozin to an established target (SGLT2) and a research target (human brain AChE). Sotagliflozin appeared more promising for SGLT2 as well as AChE-inhibition with reference to G and Ki values in comparison to Ertugliflozin. The G and Ki values for Sotagliflozin:AChE-binding were -7.16kcal/mol and 5.6M, respectively while the same were found to be -8.47kcal/mol and 0.62M, respectively for its interaction with SGLT2. Furthermore, Sotagliflozin:SGLT2-interaction was subjected to (un)binding simulation analyses by Molecular-Motion-Algorithms. This information is significant as the exact binding mode, interacting amino acid residues and simulation results for the said interaction have not been described yet. Also no X-ray crystal is available for the same. Finally, the results described herein indicate that Sotagliflozin could have an edge over Ertugliflozin for treatment of Type 2 diabetes. Future design of drugs based on Sotagliflozin scaffolds for treatment of Type 2 and/or Type 3 diabetes are highly recommended. As these drugs are still in late phases of clinical trials, the results described herein appear timely. J. Cell. Biochem. 118: 3855-3865, 2017. (c) 2017 Wiley Periodicals, Inc.