دورية أكاديمية
أعرض في EDS

Potential of Tryptamine Derivatives as Multi-Target Directed Ligands for Alzheimer's Disease: AChE, MAO-B, and COX-2 as Molecular Targets.

التفاصيل البيبلوغرافية
العنوان: Potential of Tryptamine Derivatives as Multi-Target Directed Ligands for Alzheimer's Disease: AChE, MAO-B, and COX-2 as Molecular Targets.
المؤلفون: Asghar S; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Karachi 74600, Pakistan., Mushtaq N; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi 75270, Pakistan., Ahmed A; Institute of Pharmaceutical Sciences, Jinnah Sindh Medical University, Karachi 75510, Pakistan., Anwar L; Department of Pharmacology, Faculty of Pharmacy, Hamdard University, Karachi 74600, Pakistan., Munawar R; Department of Pharmaceutical Chemistry, Dow College of Pharmacy, Dow University of Health Sciences, Karachi 74200, Pakistan., Akhtar S; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Karachi 74600, Pakistan.
المصدر: Molecules (Basel, Switzerland) [Molecules] 2024 Jan 19; Vol. 29 (2). Date of Electronic Publication: 2024 Jan 19.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, c1995-
مواضيع طبية MeSH: Monoamine Oxidase*/metabolism , Alzheimer Disease*/metabolism, Humans ; Monoamine Oxidase Inhibitors/chemistry ; Cyclooxygenase 2/metabolism ; Molecular Docking Simulation ; Cholinesterase Inhibitors/pharmacology ; Cholinesterase Inhibitors/therapeutic use ; Cholinesterase Inhibitors/chemistry ; Structure-Activity Relationship ; Tryptamines/pharmacology ; Acetylcholinesterase/metabolism ; Ligands
مستخلص: Extensive research has been dedicated to develop compounds that can target multiple aspects of Alzheimer's disease (AD) treatment due to a growing understanding of AD's complex multifaceted nature and various interconnected pathological pathways. In the present study, a series of biological assays were performed to evaluate the potential of the tryptamine analogues synthesized earlier in our lab as multi-target-directed ligands (MTDLs) for AD. To assess the inhibitory effects of the compounds, various in vitro assays were employed. Three compounds, SR42 , SR25 , and SR10, displayed significant AChE inhibitory activity, with IC 50 values of 0.70 µM, 0.17 µM, and 1.00 µM, respectively. These values superseded the standard drug donepezil (1.96 µM). In the MAO-B inhibition assay, SR42 (IC 50 = 43.21 µM) demonstrated superior inhibitory effects as compared to tryptamine and other derivatives. Moreover, SR22 (84.08%), SR24 (79.30%), and SR42 (75.16%) exhibited notable percent inhibition against the COX-2 enzyme at a tested concentration of 100 µM. To gain insights into their binding mode and to validate the biological results, molecular docking studies were conducted. Overall, the results suggest that SR42 , a 4,5 nitro-benzoyl derivative of tryptamine, exhibited significant potential as a MTDL and warrants further investigation for the development of anti-Alzheimer agents.
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فهرسة مساهمة: Keywords: Alzheimer’s disease; acetylcholinesterase (AChE) inhibitors; cyclooxygenase (COX-2) inhibitors; enzyme inhibitors; monoamine oxidase (MAO-B) inhibitors; multi-target-directed ligands (MTDLs); tryptamine derivatives
المشرفين على المادة: EC 1.4.3.4 (Monoamine Oxidase)
0 (Monoamine Oxidase Inhibitors)
EC 1.14.99.1 (Cyclooxygenase 2)
0 (Cholinesterase Inhibitors)
422ZU9N5TV (tryptamine)
0 (Tryptamines)
EC 3.1.1.7 (Acetylcholinesterase)
0 (Ligands)
تواريخ الأحداث: Date Created: 20240126 Date Completed: 20240129 Latest Revision: 20240129
رمز التحديث: 20240129
مُعرف محوري في PubMed: PMC10820890
DOI: 10.3390/molecules29020490
PMID: 38276568
قاعدة البيانات: MEDLINE
الوصف
تدمد:1420-3049
DOI:10.3390/molecules29020490