In Silico and In Vitro Analysis of Bioactive Compounds from Ficus benghalensis as a Novel Approach to Targeting Brain Abscess Pathogen.

IF 1.8 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Biochemistry and Biophysics Pub Date : 2025-07-17 DOI:10.1007/s12013-025-01823-1

Ihtesham Arshad, Maryum Zainab, Ayesha Farooq, Saira Zulfiqar, Anna Ali, Rubina Bibi, Shaista Shafiq, Imran Zafar, Muhammad Mazhar Ayaz, Yahya A Almutawif, Najeeb Ullah Khan

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引用次数: 0

Abstract

The management of brain abscesses, particularly with Escherichia coli (E. coli) in immunocompromised patients, remains contentious. This study evaluates the bioactive potential of Ficus benghalensis extracts against brain abscess pathogens, including multidrug-resistant E. coli and Staphylococcus aureus (S. aureus), through phytochemical, pharmacological, and computational analyses. High yields (75-85%) were obtained from polar solvent extraction (acetone, methanol, ethyl acetate). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 30 bioactive compounds, including myricetin, naringenin-7-O-rutinoside, and harpagoside. Methanol extracts exhibited potent antimicrobial activity with inhibition zones of 18.2 mm (E. coli) and 17.9 mm (S. aureus) and minimum inhibitory concentration (MIC) values of 210-250 µg/mL. Ex vivo assays on clinical isolates showed dose-dependent inhibition (MIC50 = 150 µg/mL). Molecular docking indicated quercetin (-7.5 kcal/mol) and kaempferol (-7.8 kcal/mol) targeting E. coli FimH and OmpA, while lupeol (-9.1 kcal/mol) and ellagic acid (-8.7 kcal/mol) targeted S. aureus PBP2a and Hla. Pharmacokinetic analysis revealed quercetin and gallic acid as lead candidates with 100% gastrointestinal (GI) absorption and bioavailability (0.55-0.56), but limited blood-brain barrier (BBB) permeability (brain score: 0.24). Three-dimensional quantitative structure-activity relationship (3D-QSAR) comparative molecular field analysis (CoMFA) models (R² = 0.111, Q² = 0.00) emphasized steric and electrostatic interactions (84%) in bioactivity. These findings suggest that Ficus benghalensis holds potential as a multitarget antimicrobial agent for brain abscess therapy, with further optimization for central nervous system (CNS) delivery needed.

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红ficus benghalensis生物活性物质作为脑脓肿病原菌的新途径的体外和体外分析。

脑脓肿的处理，特别是免疫功能低下患者的大肠杆菌（E. coli），仍然存在争议。本研究通过植物化学、药理学和计算分析来评估榕树提取物对脑脓肿病原体的生物活性潜力，包括耐多药大肠杆菌和金黄色葡萄球菌（S. aureus）。极性溶剂萃取（丙酮、甲醇、乙酸乙酯）得率高（75 ~ 85%）。液相色谱-串联质谱（LC-MS/MS）鉴定出30种生物活性化合物，包括杨梅素、柚皮素-7- o -芦丁苷和哈巴果苷。甲醇提取物对大肠杆菌和金黄色葡萄球菌的抑制范围分别为18.2 mm和17.9 mm，最小抑制浓度（MIC）为210 ~ 250µg/mL。临床分离株体外试验显示剂量依赖性抑制（MIC50 = 150µg/mL）。分子对接表明槲皮素（-7.5 kcal/mol）和山奈酚（-7.8 kcal/mol）靶向大肠杆菌FimH和OmpA，芦皮醇（-9.1 kcal/mol）和鞣花酸（-8.7 kcal/mol）靶向金黄色葡萄球菌PBP2a和Hla。药代动力学分析显示槲皮素和没食子酸是主要候选药物，具有100%的胃肠道（GI）吸收和生物利用度（0.55-0.56），但血脑屏障（BBB）渗透性有限（脑评分：0.24）。三维定量构效关系（3D-QSAR）比较分子场分析（CoMFA）模型（R2 = 0.111, Q2 = 0.00）强调空间和静电相互作用（84%）对生物活性的影响。这些发现表明，榕树具有作为脑脓肿治疗的多靶点抗菌药物的潜力，需要进一步优化中枢神经系统（CNS）的递送。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Biochemistry and Biophysics 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

7.5 months

期刊介绍： Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.