Bioactive constituents from Gardenia aqualla (Rubiaceae) stem bark as promising antibacterial agents: In vitro and in silico insights

Continuing phytochemical investigation of the methanolic extract of Gardenia aqualla stem bark led to the isolation of a new fatty acid ester, henpentacontyl acetate (1 ), together with four known compounds: trans-apo-8′-carotenoic acid (2 ), ethyl (all-E)-8′-trans-apo-β-caroten-8′-oate (3 ), D-mannitol (4 ), and 2,3,4,5,6-pentahydroxyhexyl acetate (5 ). Acetalation of D-mannitol afforded a new derivative, 1,2:5,6-di-O-isopropylidene-D-mannitol (4a ). The structures of all isolated and synthesized compounds were established by spectroscopic and spectrometric analyses and comparison with literature data. The antibacterial potential of compounds1 –5 was assessed in vitro using the microdilution method against Gram-positive and Gram-negative bacteria. Compounds2 and3 exhibited significant activity against Staphylococcus aureus ATCC700698 and S. aureus NR46003 (MIC = 8 μg/mL), while other compounds showed low to moderate effects depending on the strain. Molecular docking analysis against S. aureus pyruvate kinase demonstrated that compounds2 and3 had higher binding affinities (−11.94 kcal/mol) than ciprofloxacin (−8.54 kcal/mol) and penicillin (−8.16 kcal/mol). ADMET predictions revealed that compound1 possesses favorable pharmacokinetic and low-toxicity properties, whereas compounds2 and3 showed good drug-likeness but limited solubility. Compound4a exhibited improved pharmacokinetic parameters and an extended half-life, suggesting potential for further development. Collectively, these findings highlight the therapeutic promise of G. aqualla constituents, particularly compounds2 ,3 , and4a , as antibacterial agents for managing oral and ear infections.