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Lipoxygenase inhibitory potential of secondary metabolites isolated from Pistacia integerrima:a comprehensive in vitro analysis integrating molecular docking,ADMET and DFT studies

摘要Background:Pistacia integerrima,a cornerstone of traditional medicine,is renowned for its therapeutic applications against various health conditions,including cancer and hepatitis.This study investigates the pharmacological potential of bioactive compounds derived from Pistacia integerrima in inhibiting 5-lipoxygenase(5-LOX),a key enzyme implicated in inflammation and cancer progression.The current study aimed to evaluate the lipoxygenase inhibitory activity of bioactive compounds from Pistacia integerrima and assess their potential for therapeutic development in the context of inflammation and cancer treatment.Methods:Three major compounds-spinacetin(1),patuletin(2),and pistagremic acid(3)-were isolated from Pistacia integerrima and analyzed for their lipoxygenase inhibitory activity.Biochemical assays and molecular docking studies were performed to assess their effectiveness in inhibiting 5-LOX.Results:All three compounds demonstrated significant inhibition of lipoxygenase activity.Spinacetin(1)and patuletin(2)exhibited the most potent inhibitory effects,with IC50 values of 40.34 μM and 45.04 μM,respectively.Molecular docking studies revealed that patuletin(2)had the highest binding affinity(-7.717 kcal/mol)against 5-LOX,followed by spinacetin(1)with a binding affinity of-6.074 kcal/mol.In-depth in silico analysis highlighted the drug-likeness of spinacetin(1)and its favorable toxicological profile,suggesting its suitability for therapeutic development.Conclusion:The study demonstrates that compounds from Pistacia integerrima,particularly spinacetin and patuletin,have significant lipoxygenase inhibitory activity,with spinacetin showing promise as a lead candidate for lipoxygenase-targeted therapies.The findings reinforce the therapeutic relevance of Pistacia integerrima and suggest that its bioactive compounds may serve as safer,plant-based alternatives to conventional anti-inflammatory and anticancer treatments.

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作者 Abdur Rauf [1] Muhammad Umer Khan [2] Zuneera Akram [3] Chaudhry Ahmed Shabbir [4] Yahya Saleh Al-Awthan [5] Omar Salem Bahattab [6] Adil Abbas Hassan Mujawah [7] Hassan A.Hemeg [8] Marcello Iriti [9] 学术成果认领
作者单位 Department of Chemistry,University of Swabi,Swabi 23561,Pakistan [1] Institute of Molecular Biology and Biotechnology,The University of Lahore,Lahore 5005,Pakistan [2] Department of Pharmacology,Faculty of Pharmaceutical Sciences,Baqai Medical University,Karachi 75340,Pakistan [3] Faculty of Medical and Health Sciences,The University of Adelaide,Adelaide SA 5005,Australia [4] Department of Biology,Faculty of Science,University of Tabuk,Tabuk 71491,Saudi Arabia;Biodiversity Genomics Unit,Faculty of Science,University of Tabuk,Tabuk 71491,Saudi Arabia [5] Department of Biology,Faculty of Science,University of Tabuk,Tabuk 71491,Saudi Arabia [6] Department of Chemistry,College of Science,Qassim University,Buraidah 51452,Saudi Arabia [7] Department of Clinical Laboratory Technology,College of Applied Medical Sciences,Taibah University,P.O.Box 344,Madinah,Saudi Arabia [8] Department of Biomedical,Surgical and Dental Sciences,University of Milan,Milan 20129,Italy;National Interuniversity Consortium of Materials Science and Technology(INSTM),Firenze 50121,Italy [9]
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DOI 10.53388/TMR20241203001
发布时间 2025-09-18(万方平台首次上网日期,不代表论文的发表时间)
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