Mansour_2025_Sci.Rep_15_27206

Biotransformation of (-)-alpha-bisabolol (1) was investigated by screening twenty-two fungal strains in an effort to produce new more polar and potentially bioactive metabolites. Three fungi were selected for scale-up biotransformation: Cordyceps sinensis, Alternaria alternata and Aspergillus flavus. Five metabolites were isolated: 10beta,11-dihydroxy-alpha-bisabolol (2), Hamanasic acid A (3), 2,3-dihydro-alpha-bisabolol (4), 7-dehydroxy-10,11-epoxy-3-methylcarboxy-alpha-bisabolol (5) and 10beta,11,15-trihydroxy-alpha-bisabolol (6), with metabolites 4, 5, and 6 being newly identified. Structural elucidation was performed using spectroscopic methods. alpha-bisabolol and its metabolites were evaluated for their cyclooxygenase (COX) and acetylcholinesterase (AChE) inhibitory activities, as well as neuroprotective effects against H(2)O(2) and Abeta(1-42)-induced toxicity in SH-SY5Y cells. In vitro results showed that metabolite 5 exhibited the strongest COX-2 inhibition (IC(50) = 2.508 microM), while 2 showed AChE inhibition (IC(50) = 12.94 microM), These outcomes were more confirmed by molecular docking. Metabolites 6 and 2 demonstrated superior neuroprotective effects against H(2)O(2) and Abeta(1-42)-induced toxicity compared to alpha-bisabolol. Importantly, metabolite 2 showed pronounced AChE inhibitory activity alongside favorable ADMET attributes. These findings suggest that alpha-bisabolol and its metabolite 2 are potential candidates for the modulation of neurodegenerative diseases involving inflammation, neurotoxicity, or cholinergic dysfunction. Further in vivo investigations are mandatory to ensure the study outcomes.