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

被引：27
作者：
Hussain, Rafaqat [1 ]
Khan, Shoaib [2 ]
Ullah, Hayat [3 ]
Ali, Farhan [2 ]
Khan, Yousaf [4 ]
Sardar, Asma [1 ]
Iqbal, Rashid [5 ,6 ]
Ataya, Farid S. [7 ]
El-Sabbagh, Nasser M. [8 ]
Batiha, Gaber El-Saber [9 ]
机构：
[1] Hazara Univ, Dept Chem, Mansehra 21120, Pakistan
[2] Abbottabad Univ Sci & Technol AUST, Dept Chem, Abbottabad 22500, Pakistan
[3] Univ Okara, Dept Chem, Okara 56130, Pakistan
[4] COMSATS Univ, Dept Chem, Islamabad 45550, Pakistan
[5] Aarhus Univ, Dept Agroecol Climate & Water, Blichers 20, DK-8830 Tjele, Denmark
[6] Islamia Univ Bahawalpur, Fac Agr & Environm, Dept Agron, Bahawalpur 63100, Pakistan
[7] King Saud Univ, Coll Sci, Dept Biochem, POB 2455, Riyadh 11451, Saudi Arabia
[8] Alexandria Univ, Fac Vet Med, Dept Vet Pharmacol, Alexandria 21526, Egypt
[9] Damanhour Univ, Fac Vet Med, Dept Pharmacol & Therapeut, Damanhour 22511, Egypt
来源：
PHARMACEUTICALS | 2023年 / 16卷 / 09期
关键词：
synthesis; benzimidazole; Schiff base; SAR; AChE; BuChE and molecular docking; BIOLOGICAL EVALUATION;
D O I：
10.3390/ph16091278
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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 mu M and BuChE in the range of 131.30 +/- 9.70 to 375.80 +/- 12.80 mu M in comparison with standard Donepezil, which has IC50 values of 243.76 +/- 5.70 mu M (AChE) and 276.60 +/- 6.50 mu M (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.
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页数：20
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