Targeting Bacterial DNA Gyrase-B with Fenugreek-Derived Phytochemicals: An In Silico Strategy for Antibacterial Lead Discovery
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Abstract
Antibiotic resistance poses a major public health challenge globally. Fenugreek (Trigonella foenum-graecum) contains phytochemicals that have been studied for possible antibacterial activity. This study examines the interaction of fenugreek seed phytochemicals with DNA gyrase-B using computational methods. GC-MS was employed to identify bioactive compounds. Lipinski’s Rule of Five and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analyses were used to evaluate drug-likeness and pharmacokinetic properties. Selected ligands were docked with bacterial DNA gyrase-B using AutoDock Vina and analyzed using BIOVIA Discovery Studio. GC-MS revealed 29 compounds from the aqueous and methanolic extracts, 12 of which passed the drug -likeness screening. ADMET profiling indicated favorable ADMET profiles for several candidates. Molecular docking revealed that cyclodocosane, ethyl exhibited the highest binding affinity (-9.6 kcal/mol) against DNA gyrase-B. Although, only one specific hydrophobic interaction was observed. This hydrophobic contact involves a nonpolar amino acid residue (Leu294) in the binding pocket of the protein, key to maintaining the complex's integrity. This compound outperformed the standard drug ciprofloxacin (-9.2 kcal/mol). The result indicate that the ligand may serve as a starting point for further optimization. Fenugreek seeds contain phytochemicals with promising antibacterial potential, especially against DNA gyrase-B. Cyclodocosane, ethyl may serve as a lead compound for novel antibacterial drug development, pending further validation and optimization.
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