Synthesis of Benzimidazole–Based Analogs as Anti Alzheimer’s Disease Compounds and Their Molecular Docking Studies
Bushra Adalat,
Fazal Rahim,
Muhammad Taha,
Foziah J. Alshamrani,
El Hassane Anouar,
Nizam Uddin,
Syed Adnan Ali Shah,
Zarshad Ali,
Zainul Amiruddin Zakaria
Affiliations
Bushra Adalat
Department of Chemistry, Hazara University, Mansehra 21300, Pakistan
Fazal Rahim
Department of Chemistry, Hazara University, Mansehra 21300, Pakistan
Muhammad Taha
Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
Foziah J. Alshamrani
Neurology Department, King Fahad Hospital of University, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 34211, Saudi Arabia
El Hassane Anouar
Department of Chemistry, College of Science and Humanities in Al-Kharj, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
Nizam Uddin
Department of Chemistry, University of Karachi, Karachi 75270, Pakistan
Syed Adnan Ali Shah
Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Bandar Puncak Alam, Selangor 42300, Malaysia
Zarshad Ali
Department of Chemistry, Hazara University, Mansehra 21300, Pakistan
Zainul Amiruddin Zakaria
Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, Malaysia
We synthesized 10 analogs of benzimidazole-based thiosemicarbazide 1 (a–j) and 13 benzimidazole-based Schiff bases 2 (a–m), and characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) inhibition activities. All the synthesized analogs showed varying degrees of acetylcholinesterase and butyrylcholinesterase inhibitory potentials in comparison to the standard drug (IC50 = 0.016 and 4.5 µM. Amongst these analogs 1 (a–j), compounds 1b, 1c, and 1g having IC50 values 1.30, 0.60, and 2.40 µM, respectively, showed good acetylcholinesterase inhibition when compared with the standard. These compounds also showed moderate butyrylcholinesterase inhibition having IC50 values of 2.40, 1.50, and 2.40 µM, respectively. The rest of the compounds of this series also showed moderate to weak inhibition. While amongst the second series of analogs 2 (a–m), compounds 2c, 2e, and 2h having IC50 values of 1.50, 0.60, and 0.90 µM, respectively, showed moderate acetylcholinesterase inhibition when compared to donepezil. Structure Aactivity Relation of both synthesized series has been carried out. The binding interactions between the synthesized analogs and the enzymes were identified through molecular docking simulations.
