Benzimidazole-Based Schiff Base Hybrid Scaffolds: A Promising Approach to Develop Multi-Target Drugs for Alzheimer’s Disease-Reference-Cited by-同舟云学术

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

Published:2023-09-11 Issue:9 Volume:16 Page:1278
ISSN:1424-8247
Container-title:Pharmaceuticals
language:en
Short-container-title:Pharmaceuticals

Author:

Hussain Rafaqat¹,Khan Shoaib²^ORCID,Ullah Hayat³^ORCID,Ali Farhan²,Khan Yousaf⁴,Sardar Asma¹,Iqbal Rashid⁵⁶^ORCID,Ataya Farid S.⁷^ORCID,El-Sabbagh Nasser M.⁸,Batiha Gaber El-Saber⁹

Affiliation:

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.

Funder

King Saud University

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

Link

https://www.mdpi.com/1424-8247/16/9/1278/pdf

Reference32 articles.

1. Alzheimer’s disease and other neurodegenerative dementias in comorbidity: A clinical and neuropathological overview;Matej;Clin. Biochem.,2019

2. Alzheimer’s Association (2015). Alzheimer’s disease facts and figures. Alzheimer’s Dement. J. Alzheimer’s Assoc., 11, 332–384.

3. King, A., Bodi, I., and Troakes, C. (2020). The neuropathological diagnosis of Alzheimer’s disease-the challenges of pathological mimics and concomitant pathology. Brain Sci., 10.