Literature DB >> 25402624

Forxiga (dapagliflozin): Plausible role in the treatment of diabetes-associated neurological disorders.

Sibhghatulla Shaikh1, Syed Mohd Danish Rizvi1, Shazi Shakil2, Sania Riyaz1, Deboshree Biswas1, Roshan Jahan1.   

Abstract

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.
© 2014 International Union of Biochemistry and Molecular Biology, Inc.

Entities:  

Keywords:  Alzheimer's disease; acetylcholinesterase; dapagliflozin; sodium glucose co-transporter 2; type 2 diabetes

Mesh:

Substances:

Year:  2016        PMID: 25402624     DOI: 10.1002/bab.1319

Source DB:  PubMed          Journal:  Biotechnol Appl Biochem        ISSN: 0885-4513            Impact factor:   2.431


  16 in total

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