دورية أكاديمية
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Pharmacophore Modeling and Binding Affinity of Secondary Metabolites from Angelica keiskei to HMG Co-A Reductase.

التفاصيل البيبلوغرافية
العنوان: Pharmacophore Modeling and Binding Affinity of Secondary Metabolites from Angelica keiskei to HMG Co-A Reductase.
المؤلفون: Aulifa DL; Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Bandung 45363, Indonesia.; Study Center for Development of Pharmaceutical Preparations, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Bandung 45363, Indonesia., Amirah SR; Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Bandung 45363, Indonesia., Rahayu D; Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Bandung 45363, Indonesia., Megantara S; Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Bandung 45363, Indonesia., Muchtaridi M; Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Bandung 45363, Indonesia.
المصدر: Molecules (Basel, Switzerland) [Molecules] 2024 Jun 23; Vol. 29 (13). Date of Electronic Publication: 2024 Jun 23.
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: Angelica*/chemistry , Molecular Docking Simulation* , Hydroxymethylglutaryl CoA Reductases*/metabolism , Hydroxymethylglutaryl CoA Reductases*/chemistry, Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemistry ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Secondary Metabolism ; Protein Binding ; Plant Extracts/chemistry ; Plant Extracts/pharmacology ; Ligands ; Pharmacophore
مستخلص: Statins are cholesterol-lowering drugs with a mechanism of inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase, but long-term use can cause side effects. An example of a plant capable of reducing cholesterol levels is Angelica keiskei (ashitaba). Therefore, this study aimed to obtain suitable compounds with inhibitory activity against the HMG-CoA reductase enzyme from ashitaba through in silico tests. The experiment began with screening and pharmacophore modeling, followed by molecular docking on ashitaba's compounds, statins groups, and the native ligand was (3R,5R)-7-[4-(benzyl carbamoyl)-2-(4-fluorophenyl)-5-(1-methylethyl)-1H-imidazole-1-yl]-3,5-dihydroxyheptanoic acid (4HI). Based on the results of the molecular docking simulations, 15 hit compounds had a small binding energy (ΔG). Pitavastatin, as the comparator drug (ΔG = -8.24 kcal/mol; Ki = 2.11 µM), had a lower ΔG and inhibition constant (Ki) than the native ligand 4HI (ΔG = -7.84 kcal/mol; Ki = 7.96µM). From ashitaba's compounds, it was found that 4'-O-geranylnaringenin, luteolin, isobavachalcone, dorsmannin A, and 3'-carboxymethyl-4,2'-dihydroxy-4'-methoxychalcone have low ΔG of below -6 kcal/mol. The lowest ΔG value was found in 3'-carboxymethyl-4,2'-dihydroxy-4'-methoxy chalcone with a ΔG of -6.67 kcal/mol and Ki value of 16.66 µM, which was lower than the ΔG value of the other comparator drugs, atorvastatin (ΔG = -5.49 kcal/mol; Ki = 1148.17 µM) and simvastatin (ΔG = -6.50 kcal/mol; Ki = 22.34 µM). This compound also binds to the important amino acid residues, including ASN755D, ASP690C, GLU559D, LYS735D, LYS691C, and SER684C, through hydrogen bonds. Based on the results, the compound effectively binds to six important amino acids with good binding affinity and only requires a small concentration to reduce half of the enzyme activity.
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معلومات مُعتمدة: No. 2203/UN6.3.1/PT.00/2022 (Riset Percepatan Lektor Kepala) to Diah Lia Aulifa Universitas Padjadjaran
فهرسة مساهمة: Keywords: Angelica keiskei; HMG-CoA reductase; in silico; statins
المشرفين على المادة: EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases)
0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
0 (Plant Extracts)
0 (Ligands)
تواريخ الأحداث: Date Created: 20240713 Date Completed: 20240713 Latest Revision: 20240715
رمز التحديث: 20240715
مُعرف محوري في PubMed: PMC11243442
DOI: 10.3390/molecules29132983
PMID: 38998937
قاعدة البيانات: MEDLINE
الوصف
تدمد:1420-3049
DOI:10.3390/molecules29132983