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<p>Biotransformation of (-)-<i>α</i>-bisabolol <b>(1)</b> 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: <i>Cordyceps sinensis</i>, <i>Alternaria alternata</i> and <i>Aspergillus flavus.</i> Five metabolites were isolated: 10<i>β</i>,11-dihydroxy-<i>α</i>-bisabolol <b>(2)</b>, Hamanasic acid A <b>(3)</b>, 2,3-dihydro-<i>α</i>-bisabolol <b>(4)</b>, 7-dehydroxy-10,11-epoxy-3-methylcarboxy-<i>α</i>-bisabolol <b>(5</b>) and 10<i>β</i>,11,15-trihydroxy-<i>α</i>-bisabolol <b>(6),</b> with metabolites <b>4</b>, <b>5</b>, and <b>6</b> being newly identified. Structural elucidation was performed using spectroscopic methods. <i>α</i>-bisabolol and its metabolites were evaluated for their cyclooxygenase (COX) and acetylcholinesterase (AChE) inhibitory activities, as well as neuroprotective effects against H<sub>2</sub>O<sub>2</sub> and A<i>β</i><sub>1-42</sub>-induced toxicity in SH-SY5Y cells. In vitro results showed that metabolite <b>5</b> exhibited the strongest COX-2 inhibition (IC<sub>50</sub> = 2.508&#xa0;µM), while <b>2</b> showed AChE inhibition (IC<sub>50</sub> = 12.94&#xa0;µM), These outcomes were more confirmed by molecular docking. Metabolites <b>6</b> and <b>2</b> demonstrated superior neuroprotective effects against H<sub>2</sub>O<sub>2</sub> and A<i>β</i><sub>1-42</sub>-induced toxicity compared to <i>α</i>-bisabolol. Importantly, metabolite <b>2</b> showed pronounced AChE inhibitory activity alongside favorable ADMET attributes. These findings suggest that <i>α</i>-bisabolol and its metabolite <b>2</b> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月26日

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  • Reham Mansour,
  • Ramadan A. Eldomany,
  • Amira Mira,
  • Mohamed A. Sabry,
  • Saleh H. El-sharkawy,
  • Amal F. Soliman

摘要

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: 10β,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 10β,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 H2O2 and Aβ1-42-induced toxicity in SH-SY5Y cells. In vitro results showed that metabolite 5 exhibited the strongest COX-2 inhibition (IC50 = 2.508 µM), while 2 showed AChE inhibition (IC50 = 12.94 µM), These outcomes were more confirmed by molecular docking. Metabolites 6 and 2 demonstrated superior neuroprotective effects against H2O2 and Aβ1-42-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.