دورية أكاديمية
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Structure-Based Virtual Screening and Molecular Dynamics Simulation Assessments of Depsidones as Possible Selective Cannabinoid Receptor Type 2 Agonists.

التفاصيل البيبلوغرافية
العنوان: Structure-Based Virtual Screening and Molecular Dynamics Simulation Assessments of Depsidones as Possible Selective Cannabinoid Receptor Type 2 Agonists.
المؤلفون: Mohamed GA; Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Omar AM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.; Center for Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah 21589, Saudi Arabia., AlKharboush DF; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Fallatah MA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.; King Abdulaziz Medical City, Jeddah 21423, Saudi Arabia., Sindi IA; Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia., El-Agamy DS; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt., Ibrahim SRM; Department of Chemistry, Preparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia.; Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
المصدر: Molecules (Basel, Switzerland) [Molecules] 2023 Feb 13; Vol. 28 (4). Date of Electronic Publication: 2023 Feb 13.
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: Cannabinoid Receptor Agonists*/chemistry , Molecular Dynamics Simulation*, Receptor, Cannabinoid, CB2 ; Acetylcholinesterase ; Ligands ; Receptor, Cannabinoid, CB1 ; Molecular Docking Simulation
مستخلص: The discovery of natural drug metabolites is a leading contributor to fulfilling the sustainable development goal of finding solutions to global health challenges. Depsidones are a class of polyketides that have been separated from lichens, fungi, sponges, and plants and possess various bioactivities, including cytotoxic, antimicrobial, antimalarial, antituberculosis, acetylcholinesterase and α-glucosidase inhibition, and anti-inflammatory effects. Endocannabinoid receptors (CB1 and CB2) are G-protein-coupled receptors (GPCRs), and their activation mediates many physiological processes. CB1 is the dominant subtype in the central nervous system, while CB2 is mainly expressed in the immune system. The two receptors exhibit high heterogeneity, making developing selective ligands a great challenge. Attempts to develop CB2 selective agonists for treating inflammatory diseases and neuropathic pain have not been successful due to the high homology of the binding sites of the CB receptors. In this work, 235 depsidones from various sources were investigated for the possibility of identifying CB2-selective agonists by performing multiple docking studies, including induced fit docking and Prime/molecular mechanics-generalized Born surface area (MM-GBSA) calculations to predict the binding mode and free energy. Simplicildone J ( 10 ), lobaric acid ( 110 ), mollicellin Q ( 101 ), garcinisidone E ( 215 ), mollicellin P ( 100 ), paucinervin Q ( 149 ), and boremexin C ( 161 ) had the highest binding scores (-12.134 kcal/mol, -11.944 kcal/mol, -11.479 kcal/mol, -11.394 kcal/mol, -11.322 kcal/mol, -11.305 kcal/mol, and -11.254 kcal/mol, respectively) when screened against the CB2 receptor (PDB ID: 6KPF). The molecular dynamic simulation was performed on the compounds with the highest binding scores. The computational outcomes show that garcinisidone E ( 215 ) and paucinervin Q ( 149 ) could be substantial candidates for CB2 receptor activation and warrant further in vivo and in vitro investigations.
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معلومات مُعتمدة: KEP-MSc: 27-166-1443 The Deanship of Scientific Research (DSR) at King Abdulaziz University (KAU), Jeddah, Saudi Arabia has funded this project, under grant no. (KEP-MSc: 27-166-1443)
فهرسة مساهمة: Keywords: CB2 agonist; cannabinoid receptors; depsidones; drug discovery; molecular docking; molecular dynamics; sustainable development goals
المشرفين على المادة: 0 (Cannabinoid Receptor Agonists)
3580-77-6 (depsidone)
0 (Receptor, Cannabinoid, CB2)
EC 3.1.1.7 (Acetylcholinesterase)
0 (Ligands)
0 (Receptor, Cannabinoid, CB1)
تواريخ الأحداث: Date Created: 20230225 Date Completed: 20230228 Latest Revision: 20230301
رمز التحديث: 20230301
مُعرف محوري في PubMed: PMC9965315
DOI: 10.3390/molecules28041761
PMID: 36838749
قاعدة البيانات: MEDLINE
الوصف
تدمد:1420-3049
DOI:10.3390/molecules28041761