LAUSR

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 (ΔASA)‐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 ΔG and Ki values in comparison to Ertugliflozin. The ΔG and Ki values for “Sotagliflozin:AChE‐binding” were −7.16 kcal/mol and 5.6 μM, respectively while the same were found to be −8.47 kcal/mol and 0.62 μM, 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. © 2017 Wiley Periodicals, Inc.