In vitro and in silico neuroprotective evaluation of new biotransformation metabolites of (-)-α-bisabolol

Abstract

Abstract Biotransformation of (-)- α -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: 10 β ,11-dihydroxy- α -bisabolol (2) , Hamanasic acid A (3) , 2,3-dihydro- α -bisabolol (4) , 7-dehydroxy-10,11-epoxy-3-methylcarboxy- α -bisabolol (5 ) and 10 β ,11,15-trihydroxy- α -bisabolol (6), with metabolites 4 , 5 , and 6 being newly identified. Structural elucidation was performed using spectroscopic methods. α -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 A β 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 µM), while 2 showed AChE inhibition (IC 50 = 12.94 µM), These outcomes were more confirmed by molecular docking. Metabolites 6 and 2 demonstrated superior neuroprotective effects against H 2 O 2 and A β 1-42 -induced toxicity compared to α -bisabolol. Importantly, metabolite 2 showed pronounced AChE inhibitory activity alongside favorable ADMET attributes. These findings suggest that α -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.