title: Prediction of Anti-Diabetic Drugs as Dual Inhibitors Against Acetylcholinesterase and Beta-Secretase: A Neuroinformatics Study.
abstract: An increasing number of research evidences indicate linkage between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD); the two most common diseases of aging. In addition, T2DM and AD also share some common pathophysiological features. Therefore, dual therapy that targets both the diseases can be regarded as a beneficial approach. Acetylcholinesterase (AChE) and beta-secretase (BACE) have been considered as potential therapeutic targets for AD. Accordingly, the piece of work presented here describes the binding of anti-diabetic drugs (Jardiance, Suiny and Nesina) with AChE and BACE so as to further investigate connecting bridges concerning the treatment of these two diseases. We have used "Autodock 4.2" for docking experiments. Both, hydrogen bond and hydrophobic interactions were found to be involved in the proper positioning of these diabetic drugs within the catalytic site (CAS) of AChE and BACE enzymes to permit docking. Free energy of binding (ΔG) for 'Jardiance-AChE', 'uiny-AChE' and 'Nesina-AChE' CAS interactions were found to be -9.21, -7.32 and -10.66 kcal/mol, respectively; while for 'Jardiance-BACE', 'Suiny -BACE' and 'Nesina-BACE' CAS interactions the same were determined to be -8.91, -8.58 and -10.40 kcal/mol, respectively. Hence, these diabetic drugs might act as potent dual inhibitors for the treatment of diabetes-associated neurological disorders. Consequently, the results described herein may form the basis of future dual therapy against the same.
authors.forename: Sibhghatulla
authors.initials: S
authors.lastname: Shaikh
authors.forename: Syed Mohd Danish
authors.initials: SM
authors.lastname: Rizvi
authors.forename: Tabinda
authors.initials: T
authors.lastname: Suhail
authors.affiliation: Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia. shazibiotech@gmail.com.
authors.forename: Shazi
authors.initials: S
authors.lastname: Shakil
authors.forename: Adel M
authors.initials: AM
authors.lastname: Abuzenadah
authors.forename: Rukhsar
authors.initials: R
authors.lastname: Anis
authors.forename: Deeba
authors.initials: D
authors.lastname: Naaz
authors.forename: Ashraf
authors.initials: A
authors.lastname: Dallol
authors.forename: Mohd
authors.initials: M
authors.lastname: Haneef
authors.forename: Adnan
authors.initials: A
authors.lastname: Ahmad
authors.forename: Latafat
authors.initials: L
authors.lastname: Choudhary
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D019295:Computational Biology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000627:therapeutic use; D008958:Models, Molecular
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D000110:Acetylcholinesterase; D053829:Amyloid Precursor Protein Secretases