دورية أكاديمية
Inhibition of the Janus kinase protein (JAK1) by the A. Pyrethrum Root Extract for the treatment of Vitiligo pathology. Design, Molecular Docking, ADME-Tox, MD Simulation, and in-silico investigation.
| العنوان: | Inhibition of the Janus kinase protein (JAK1) by the A. Pyrethrum Root Extract for the treatment of Vitiligo pathology. Design, Molecular Docking, ADME-Tox, MD Simulation, and in-silico investigation. |
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| المؤلفون: | Ouabane M; Molecular Chemistry and Natural Substances Laboratory, Department of Chemistry, Faculty of Science, My Ismail University, B.P. 11202, Meknes, 50000, Morocco; Chemistry-Biology Applied to the Environment URL CNRT 13, Department of Chemistry, Faculty of Science, My Ismail University, B.P. 11202, Meknes, 50000, Morocco., Zaki K; Molecular Chemistry and Natural Substances Laboratory, Department of Chemistry, Faculty of Science, My Ismail University, B.P. 11202, Meknes, 50000, Morocco., Zaki H; Biotechnology, Bioresources, And Bioinformatics Laboratory at the Higher School of Technology, 54000, Khenifra, Morocco., Guendouzi A; Laboratory of Chemistry, Synthesis, Properties and Applications, Department of Chemistry, Faculty of Science, University of Saida, Algeria., Sbai A; Molecular Chemistry and Natural Substances Laboratory, Department of Chemistry, Faculty of Science, My Ismail University, B.P. 11202, Meknes, 50000, Morocco., Sekkate C; Chemistry-Biology Applied to the Environment URL CNRT 13, Department of Chemistry, Faculty of Science, My Ismail University, B.P. 11202, Meknes, 50000, Morocco., Lakhlifi T; Molecular Chemistry and Natural Substances Laboratory, Department of Chemistry, Faculty of Science, My Ismail University, B.P. 11202, Meknes, 50000, Morocco., Bouachrine M; Molecular Chemistry and Natural Substances Laboratory, Department of Chemistry, Faculty of Science, My Ismail University, B.P. 11202, Meknes, 50000, Morocco. Electronic address: m.bouachrine@umi.ac.ma. |
| المصدر: | Computers in biology and medicine [Comput Biol Med] 2024 Sep; Vol. 179, pp. 108816. Date of Electronic Publication: 2024 Jul 01. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 1250250 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0534 (Electronic) Linking ISSN: 00104825 NLM ISO Abbreviation: Comput Biol Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York : Elsevier Original Publication: New York, Pergamon Press. |
| مواضيع طبية MeSH: | Molecular Docking Simulation* , Vitiligo*/drug therapy , Vitiligo*/metabolism , Plant Extracts*/chemistry , Plant Extracts*/therapeutic use , Molecular Dynamics Simulation* , Plant Roots*/chemistry , Janus Kinase 1*/chemistry , Janus Kinase 1*/metabolism , Janus Kinase 1*/antagonists & inhibitors, Humans |
| مستخلص: | This study delves into the therapeutic efficacy of A. pyrethrum in addressing vitiligo, a chronic inflammatory disorder known for inducing psychological distress and elevating susceptibility to autoimmune diseases. Notably, JAK inhibitors have emerged as promising candidates for treating immune dermatoses, including vitiligo. Our investigation primarily focuses on the anti-vitiligo potential of A. pyrethrum root extract, specifically targeting N-alkyl-amides, utilizing computational methodologies. Density Functional Theory (DFT) is deployed to meticulously scrutinize molecular properties, while comprehensive evaluations of ADME-Tox properties for each molecule contribute to a nuanced understanding of their therapeutic viability, showcasing remarkable drug-like characteristics. Molecular docking analysis probes ligand interactions with pivotal site JAK1, with all compounds demonstrating significant interactions; notably, molecule 6 exhibits the most interactions with crucial inhibition residues. Molecular dynamics simulations over 500ns further validate the importance and sustainability of these interactions observed in molecular docking, favoring energetically both molecules 6 and 1; however, in terms of stability, the complex with molecule 6 outperforms others. DFT analyses elucidate the distribution of electron-rich oxygen atoms and electron-poor regions within heteroatoms-linked hydrogens. Remarkably, N-alkyl-amides extracted from A. pyrethrum roots exhibit similar compositions, yielding comparable DFT and Electrostatic Potential (ESP) results with subtle distinctions. These findings underscore the considerable potential of A. pyrethrum root extracts as a natural remedy for vitiligo. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024. Published by Elsevier Ltd.) |
| فهرسة مساهمة: | Keywords: A. pyrethrum, N-Alkyl-amides; ADME-Tox; And molecular docking; DFT; JAK1 |
| المشرفين على المادة: | 0 (Plant Extracts) EC 2.7.10.2 (Janus Kinase 1) EC 2.7.10.2 (JAK1 protein, human) |
| تواريخ الأحداث: | Date Created: 20240702 Date Completed: 20240814 Latest Revision: 20240814 |
| رمز التحديث: | 20240814 |
| DOI: | 10.1016/j.compbiomed.2024.108816 |
| PMID: | 38955123 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1879-0534 |
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| DOI: | 10.1016/j.compbiomed.2024.108816 |