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

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.