Phytochemical Composition, Antimicrobial Activity, and In Silico Evaluation of Azadirachta indica Stem Bark Extracts against Multidrug-Resistant Pathogens

Abstract

Introduction: Medicinal plants are valuable sources of bioactive compounds with therapeutic potential. This study aimed to profile the bioactive compounds in the stem bark of Azadirachta indica, evaluate the antimicrobial activity of its crude and fractionated extracts, and explore molecular interactions with key bacterial enzymes.

Methods: Crude stem bark extracts were obtained via maceration and fractionated using n-hexane and ethanol. Antimicrobial activity was assessed against multidrug-resistant pathogens using standard microbiological assays. Phytochemical composition was analyzed via high-performance liquid chromatography (HPLC), while molecular docking, ADME predictions, drug-likeness, and toxicity assessments were performed in silico.

Results: The crude extract displayed broad antibacterial activity, with inhibition zones of 10–20 mm at 100 mg/mL, showing strongest activity against Acinetobacter baumannii. Fractionated extracts exhibited moderate activity (6–12 mm). MIC values ranged from 50–100 mg/mL for the crude extract and ≥100 mg/mL for fractions. HPLC identified key compounds including quercetin, rutin hydrate, kaempferol, gallic acid and sinapic acid. Docking studies showed rutin hydrate, quercetin, nicotiflorin, and astragalin had high binding affinities for E. coli DNA gyrase B and A. baumannii topoisomerase IV. ADME predictions indicated good gastrointestinal absorption for most compounds, with minimal toxicity and generally favorable drug-likeness profiles, except for rutin hydrate and nicotiflorin.