Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Designing dual inhibitors for the treatment of Alzheimer’s disease as well as Type 2 diabetes mellitus via pharmacoinformatics approach: A step towards better medication for diabetes-associated neurological disorder

Talib Hussain¹ , Syed Mohd Danish Rizvi², Gehad M Subaiea¹, Abulrahman Sattam Alanazi³, Afrasim Moin²

¹Department of Pharmacology and Toxicology; ²Department of Pharmaceutics; ³Department of Clinical Pharmacy, College of Pharmacy, University of Hail, Hail, Kingdom of Saudi Arabia.

For correspondence:- Talib Hussain Email: mdth_ah@yahoo.com

Accepted: 20 May 2020 Published: 30 June 2020

Citation: Hussain T, Rizvi SM, Subaiea GM, Alanazi AS, Moin A. Designing dual inhibitors for the treatment of Alzheimer’s disease as well as Type 2 diabetes mellitus via pharmacoinformatics approach: A step towards better medication for diabetes-associated neurological disorder. Trop J Pharm Res 2020; 19(6):1233-1242 doi: 10.4314/tjpr.v19i6.18

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To design dual inhibitors against Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) via pharmacoinformatics approach.

Methods: Dual Drug Candidates (DDC) were designed and explored for their molecular interaction with several AD and T2DM targets. Pterostilbene, a natural anti-T2DM compound was coupled with different cholinesterase inhibitors to design DDC. Orisis Datawarrior online property calculator tools, Autock 4.2 and Hex 5.1 were used to investigate the potency of all DDC relative to positive controls.

Results: The study found that DDC2 (pterostilbene - methylene linker -octa hydro amino phenothiazine), DDC3 (pterostilbene - ethylene linker - N-phthalimide) and DDC5 (pterostilbene - carbonyl linker - 2-methyl-4-aminoquinoline) were the most promising out of all the DDCs. DDC2 showed strong molecular interaction with most of the AD and T2DM targets, including acetylcholinesterase, butrylcholinesterase, β-secretase, receptor for advanced glycation end products and ATP sensitive potassium channel, dipeptidyl peptidase IV and sodium glucose transport protien 2. The findings also revealed the amyloid anti-aggregation potential of DDC.

Conclusion: The results show that DDC3 and DDC5 significantly interfer with the primary nucleation process of β amyloid. Thus, DDC2, DDC3 and DDC5 have strong anti-T2DM and anti-AD potential.

Keywords: Type 2 Diabetes Mellitus, Alzheimer’s disease, Dual drug candidate, Amyloid-beta, Pterostilbene