Antimicrobial resistance (AMR) poses a severe and escalating threat to global public health, directly attributed to approximately 1.27 million deaths in 2019, with projections estimating 39 million cumulative deaths between 2025 and 2050. This study investigated the in-vitro antibacterial activity, GC-MS phytochemical profile, and in-silico molecular docking potential of the crude ethanolic stem-bark extract of Cassia fistula L. (CFSE) against five clinically significant pathogens. The extract was prepared by cold maceration of 200 g of pulverized stem-bark in 1000 mL of absolute ethanol for 72 h, yielding 21.08% (w/w), and tested at 12.5–100% (v/v) using the Kirby-Bauer disc diffusion method. GC-MS analysis was performed using a Shimadzu GCMS-QP2010 system, while molecular docking was conducted against ten resistance-associated bacterial protein targets using Schrödinger-Maestro GLIDE, with binding free energies estimated via Prime MM-GBSA. CFSE demonstrated concentration-dependent activity against E. coli and marginal activity against P. aeruginosa at 100%, with no activity against remaining pathogens. GC-MS identified 24 compounds, dominated by resorcinol, 4- O -methylmannose, and methyl α-D-mannofuranoside. In the molecular docking study, three GC-MS-identified compounds emerged as the most promising leads across the ten bacterial protein targets. Resorcinol achieved the strongest binding at penicillin-binding protein 4 of S. aureus (docking score: − 6.99 kcal/mol) and Klebsiella LpxH (− 6.66 kcal/mol), surpassing the respective standard drugs at both targets. 1,6-anhydro-4- O -methyl-D-glucopyranose demonstrated the broadest activity across all ten targets, outperforming standard drugs including avibactam and trimethoprim in docking score and/or binding free energy (MM-GBSA) at multiple targets. Methyl α- D -mannofuranoside recorded the most thermodynamically favorable binding energy overall at KPC-44 carbapenemase of K. pneumoniae , exceeding both avibactam and clavulanate. All three lead compounds satisfied Lipinski’s drug-likeness criteria, displayed favorable gastrointestinal absorption, and did not inhibit major cytochrome P 450 enzymes. These findings support further bioactivity-guided fractionation of C. fistula stem-bark for antimicrobial drug discovery.
Mohammed et al. (Fri,) studied this question.