Phytochemical Profiling, Pharmacokinetics, and Antimicrobial Activity of Azadirachta indica Leaf Extracts: In Silico and In Vitro Evaluations
DOI:
https://doi.org/10.56919/usci.2544.015Keywords:
Azadirachta indica, GC-MS, ADMET, Phytochemicals, Antimicrobial resistance, Lipinski's rule of fiveAbstract
Antimicrobial resistance (AMR) is a critical global health threat, necessitated by the rise of multidrug-resistant "superbugs" and a lack of new antibiotic discovery. Plant-derived phytochemicals, particularly from Azadirachta indica (neem), offer a promising reservoir of bioactive molecules with broad-spectrum therapeutic potential. This study aimed to characterize the bioactive profiles of aqueous and methanolic leaf extracts and evaluate their therapeutic potential against viral, bacterial, and fungal targets. Dried A. indica leaves were processed into powder and subjected to three-day maceration in methanol and water. Phytochemicals were identified through qualitative screening and Gas Chromatography-Mass Spectrometry (GC–MS) using a SHIMADZU GCMS-QP2010 PLUS system. Pharmacokinetic profiles and drug-likeness were predicted via SwissADME and ADMETLab 3.0. Molecular docking simulations were performed using AutoDock Vina against nine pathogenic targets, while in vitro efficacy was determined through well/disk diffusion and MIC/MBC/MFC assays. The aqueous extract provided a significantly higher yield (10.78%) than the methanolic extract (10.58%, p = 0.013). GC-MS identified 17 compounds in the methanolic extract (linoleic acid dominant) and 21 in the aqueous extract (oleic acid dominant). Molecular docking revealed that Methyl linolelaidate had the highest affinity for HIV Reverse Transcriptase (-6.9 kcal/mol), while Monopalmitin and Linoleoyl chloride showed strong binding to fungal and bacterial targets (-6.0 kcal/mol). Antimicrobial testing confirmed concentration-dependent activity, with the methanolic extract achieving a 15.6 mm zone of inhibition against S. epidermidis. ADMET analysis identified monopalmitin, resorcinol, and methyl caprate as the most viable drug candidates. A. indica is a potent source of bioactive molecules capable of disrupting microbial membranes and inhibiting key enzymes. While the findings support the therapeutic potential of these compounds, predicted nephrotoxicity for methyl vaccenate and methyl caprate underscores the need for further experimental validation to ensure clinical safety.
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