Forxiga (dapagliflozin): Plausible role in the treatment of diabetes-associated neurological disorders.
Numerous clinical and epidemiological studies have provided direct evidence to strengthen the link between type 2 diabetes (T2D) and Alzheimer's disease (AD). The possibility that T2D patients might be at increased risk in developing AD has serious societal implications. Sodium glucose co-transporter 2 (SGLT2) is one of the best targets in the treatment of diabetes, whereas acetylcholinesterase (AChE) has long been regarded as a therapeutic target for AD. This study explores the molecular interactions between AChE and SGLT2 with a new US Food and Drug Administration approved antidiabetic drug Forxiga (dapagliflozin) to explore a possible link between the treatments of AD and diabetes. Docking study was performed using "Autodock4.2." Hydrophobic and cation-π interactions play an important role in the correct positioning of dapagliflozin within the catalytic site (CAS) of SGLT2 and AChE enzymes to permit docking. Free energy of binding (ΔG) of "dapagliflozin-SGLT2" and "dapagliflozin-CAS domain of AChE" interactions was found to be -6.25 and -6.28 kcal/mol, respectively. Hence, dapagliflozin might act as a potent dual inhibitor of SGLT2 and AChE. The results described herein may form the basis of future dual therapy against diabetes-associated neurological disorders.
Department of Biosciences, Integral University, Lucknow, India.
Sibhghatulla
S
Shaikh
Department of Biosciences, Integral University, Lucknow, India.
Syed Mohd Danish
SM
Rizvi
Department of Bioengineering, Integral University, Lucknow, India.
Shazi
S
Shakil
Department of Biosciences, Integral University, Lucknow, India.
Sania
S
Riyaz
Department of Biosciences, Integral University, Lucknow, India.
Deboshree
D
Biswas
Department of Biosciences, Integral University, Lucknow, India.
Roshan
R
Jahan
D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D001559:Benzhydryl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D062105:Molecular Docking Simulation; D009422:Nervous System Diseases / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors
D001559:Benzhydryl Compounds; D002800:Cholinesterase Inhibitors; D005960:Glucosides; D007004:Hypoglycemic Agents; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C529054:dapagliflozin; D000110:Acetylcholinesterase
Alzheimer's disease; acetylcholinesterase; dapagliflozin; sodium glucose co-transporter 2; type 2 diabetes