Benzimidazole-Based Schiff Base Hybrid Scaffolds: A Promising Approach to Develop Multi-Target Drugs for Alzheimer's Disease

Rafaqat Hussain; Shoaib Khan; Hayat Ullah; Farhan Ali; Yousaf Khan; Asma Sardar; Rashid Iqbal; Farid S Ataya; Nasser M El-Sabbagh; Gaber El-Saber Batiha

doi:10.3390/ph16091278

Benzimidazole-Based Schiff Base Hybrid Scaffolds: A Promising Approach to Develop Multi-Target Drugs for Alzheimer's Disease

Pharmaceuticals (Basel). 2023 Sep 11;16(9):1278. doi: 10.3390/ph16091278.

Authors

Affiliations

¹ Department of Chemistry, Hazara University, Mansehra 21120, Pakistan.
² Department of Chemistry, Abbottabad University of Science and Technology (AUST), Abbottabad 22020, Pakistan.
³ Department of Chemistry, University of Okara, Okara 56130, Pakistan.
⁴ Department of Chemistry, COMSATS University, Islamabad 45550, Pakistan.
⁵ Department of Agroecology-Climate and Water, Aarhus University, Blichers Allé 20, 8830 Tjele, Denmark.
⁶ Department of Agronomy, Faculty of Agriculture and Environment, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
⁷ Department of Biochemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
⁸ Department of Veterinary Pharmacology, Faculty of Veterinary Medicine, Alexandria University, Alexandria 21526, Egypt.
⁹ Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, AlBeheira, Egypt.

Abstract

A series of benzimidazole-based Schiff base derivatives (1-18) were synthesized and structurally elucidated through ¹H NMR, ¹³C NMR and HREI-MS analysis. Subsequently, these synthetic derivatives were subjected to evaluation for their inhibitory capabilities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). All these derivatives showed significant inhibition against AChE with an IC₅₀ value in the range of 123.9 ± 10.20 to 342.60 ± 10.60 µM and BuChE in the range of 131.30 ± 9.70 to 375.80 ± 12.80 µM in comparison with standard Donepezil, which has IC₅₀ values of 243.76 ± 5.70 µM (AChE) and 276.60 ± 6.50 µM (BuChE), respectively. Compounds 3, 5 and 9 exhibited potent inhibition against both AChE and BuChE. Molecular docking studies were used to validate and establish the structure-activity relationship of the synthesized derivatives.

Keywords: AChE; BuChE and molecular docking; SAR; Schiff base; benzimidazole; synthesis.

Grants and funding

This research was funded by King Saud University (Riyadh, Saudi Arabia) for funding this research through Researchers supporting Project number (RSPD2023-R693).