Molecular docking, synthesis and biological evaluation of phenacyl derivatives of 9-aminoacridine as anti-Alzheimer's agent.

Autor:	Munawar R; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Pakistan/ Department of Pharmaceutical Chemistry, Dow College of Pharmacy, Dow University of Health Sciences, Karachi, Pakistan., Mushtaq N; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Pakistan., Ahmad A; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Pakistan/ Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, Jinnah Sindh Medical University, Karachi, Pakistan., Saeed SMG; Department of Food Science and Technology, University of Karachi, Karachi, Pakistan., Usmani S; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Pakistan/Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, Jinnah Sindh Medical University, Karachi, Pakistan., Akhtar S; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Karachi, Pakistan., Saify ZS; HEJ Research Institute of Chemistry, University of Karachi, Karachi, Pakistan., Arif M; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Karachi, Pakistan., Akram A; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Federal Urdu University Arts, Science and Technology, Karachi, Pakistan.
Jazyk:	angličtina
Zdroj:	Pakistan journal of pharmaceutical sciences [Pak J Pharm Sci] 2020 Mar; Vol. 33 (2), pp. 659-668.
Abstrakt:	Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder mainly characterized by progressive deterioration of memory and impaired cognitive function. The most promising approach for symptomatic relief of AD is to inhibit acetylcholinesterase (AChE). On the basis of this approach in-house library of 9-aminoacridine derivatives were constructed and allowed to docked against human acetylcholinesterase (hAChE) (PDB ID: 4EY7), using MOE 2018.01 and PyRx 0.9.2 (AutoDock Vina). Top ranked and best fitted molecules were synthesized by targeting the 9-amino group of aminoacridine with substituted phenacyl halides. Anti-Alzheimer's potential was checked by in vitro AChE inhibition, antioxidant activity (DPPH scavenging ability) and fibril disaggregation. Subjected ligands suggested as promising multitargeted candidate with pronounced results in term of IC 50 values (AChE inhibition 2.400-26.138μM), however, none of them showed potential towards fibril inhibition.
Databáze:	MEDLINE
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