Synthesis of Pyrazoline derivatives, condensation of β-dicarbonyl compounds with isoniazid (INH), and their biological evaluation as multitarget anti-Alzheimer' disease agents

被引:2
作者
Kanwal, Madiha [1 ,4 ]
Sarwar, Sadia [2 ]
Nadeem, Humaira [1 ]
Zafar, Rehman [3 ]
Rahman, Khondaker Miraz [4 ]
机构
[1] Riphah Int Univ, Riphah Inst Pharmaceut Sci, Dept Pharmaceut Chem, Islamabad 44000, Pakistan
[2] Riphah Int Univ, Riphah Inst Pharmaceut Sci, Dept Pharmacol & Therapeut, Islamabad 44000, Pakistan
[3] Akhtar Saeed Med Coll, Akhtar Saeed Coll Pharm, Islamabad 44000, Pakistan
[4] Kings Coll London, Inst Pharmaceut Sci, Franklin Wilkins Bldg,150 Stamford St, London SE1 9NH, England
关键词
Alzheimer; Pyrazoline derivatives; Molecular docking; Acetylcholine esterase (AChE); Butyrylcholine esterase (BChE); Anti-oxidant; MOLECULAR DOCKING; ANTIDEPRESSANT; INHIBITORS; ANTITUMOR; DESIGN; SERIES;
D O I
10.1007/s11696-023-03224-1
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Alzheimer's disease is a complex and progressive form of dementia. Its treatment relies on the behavioral and cognitive symptoms of an individual. Inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is a primary strategy used for treating Alzheimer's disease. Pyrazoline is a well-recognized nitrogen-containing five-membered heterocyclic skeleton. The unique structure of pyrazoline gives it a spatial configuration that leads to the multiple substitution pattern and advanced pharmacological properties. In an attempt to identify potent acetylcholine (AChE) and butyrylcholinesterase (BChE) inhibitors, new pyrazoline derivatives (IIIa-IIId) were synthesized using conventional method. The synthesised compounds were purified by column chromatography and were analysed using LCMS, 1HNMR, 13CNMR, and Mass Spectroscopic HR-MS techniques. The derivatives underwent initial screening for in-vitro antioxidant potential. The most potent compound, IIIa, showed IC50 values of 22.15 and 25.09 nM against AChE and BChE, respectively. Additionally, in-silico screening with AutoDock tools indicated that IIIa had promising binding affinities to the targets, with a binding energy (- 8.9 kcal/mol) comparable to donepezil (- 10.6 kcal/mol). The binding pattern of IIIa to AChE's active site justified its in-vitro inhibitory activity. These findings suggest that compound IIIa has potential as a new therapeutic agent for Alzheimer's disease and is suitable for pre-clinical evaluation.
引用
收藏
页码:2033 / 2042
页数:10
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