پتانسیل یک ترکیب طبیعی بر علیه اختلالات عصبی: مطالعه مجازی آرتوفلاوانوکومارین به عنوان مهار کننده بتا-سکرتاز 1

رزاقی اصل, نیما and کریمی, ادیبه and عبادی, احمد (1397) پتانسیل یک ترکیب طبیعی بر علیه اختلالات عصبی: مطالعه مجازی آرتوفلاوانوکومارین به عنوان مهار کننده بتا-سکرتاز 1. Computational Biology and Chemistry ــ 77 . pp. 307-317. شاپا 1476-9271

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Official URL: https://www.sciencedirect.com/science/article/pii/...


The potential of natural product vs neurodegenerative disorders: In silico study of artoflavanocoumarin as BACE-1 inhibitor

English Abstract

Abstract Increasing evidence suggests the beneficial impact of flavonoid-rich nutrition on normal cognitive function. It has been revealed that flavonoids can slow neurodegenerative processes in situations such as Alzheimer’s disease (AD). The β-secretase (BACE-1) is one of the most studied targets in AD therapy owing to its role in producing Aβ plaques. In fact the unique role of BACE-1 in pathogenesis of neurodegenerative diseases has made it a druggable target to develop anti-AD agents. Taking into account the anti-amyloidogenic and anti-oxidative properties, flavonoids have received considerable attention as lead candidates for anti-AD drug discovery projects. In continuation to our interest toward rational exploration of potential anti-AD agents, it was attempted to conduct a combined structure based in silico study and explore pharmacophore of a flavanocoumarin derivative as BACE-1 Inhibitor. Ab initio studies showed that both pseudo-axial and pseudo-equatorial conformers could convert to each other freely at room temperature. Within this study it was revealed that artoflavanocoumarin possess essential pharmacophoric groups to inhibit BACE-1. Considering four different protonation states of BACE-1 as di-deprotonated, diprotonated, protonated Asp32 and protonated Asp228, it was also found that affinity of artoflavanocoumarin toward different protonation states of BACE-1could be ranked as Asp32p-Asp228i > di-deprotonated ∼ Asp32i-Asp228p >> diprotonated. PMF study on artoflavanocoumarin showed that it could pass 1.8 kcal/mol free energy barrier from water to DPPC lipid bilayer. Moreover the pros and cons of artoflavanocoumarin as a lead compound were elucidated.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :نیما رزاقی اصل
نویسنده :ادیبه کریمی
نویسنده مسئول :احمد عبادی
Additional Information:Impact Factor (2017) 1.412 Indexed in: ISI, Pubmed/Medline/Index Medicus, Scopus, Chemical Abstracts, EMBiology, Chemical Engineering Biotechnology Abstracts, BIOSIS, Cambridge Scientific Abstracts
کلیدواژه ها (انگلیسی):Alzheimer’s disease - BACE-1 - Natural products - Artoflavanocoumarin - In silico study
Subjects:QV pharmacology > QV 744 Medicinal Chemistry
Divisions:School of Pharmacy > Department of Medicinal Chemistry
ID Code:10824
Deposited By: Dr Nima Razzaghi-Asl
Deposited On:24 Aug 1397 12:37
Last Modified:24 Aug 1397 12:37

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