Acetylcholinesterase and butyrylcholinesterase inhibition by nectriapyrone and tryptophol isolated from endophytic fungus Phomopsis sp.

Abstract

Cholinesterase (ChE) inhibitors are currently the main drugs used to treat the cognitive symptoms of Alzheimer’s disease (AD). Dual cholinesterase inhibitors, that is, compounds capable of inhibiting both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), are considered a new potential approach for the long-term treatment of patients with AD. We evaluated the ethyl acetate extract of Phomopsis sp., grown in liquid medium malt extract and potato dextrose (PDB), an endophyte isolated from the Brazilian medicinal plant Hancornia speciosa. The anticholinesterase (AChE) and butyrylcholinesterase (BuChE) activities were evaluated. The extracts exhibited dual action against AChE and BuChE. The compounds isolated from these extracts, nectriapyrone (1) and tryptophol (2), showed inhibitory action on BuChE (IC50 = 29.05 and 34.15 μM respectively), being selective towards BuChE. The discovery of selective BuChE inhibitors is extremely important for the development of drugs that can be used in the treatment of patients diagnosed with AD.

Graphical Abstract

Keywords:

• Endophytic fungus
• Phomopsis sp.
• Alzheimer’s disease
• anticholinesterase activity
• butyrylcholinestrase

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors are grateful to CAPES, CNPq, and the State of São Paulo Research Foundation (FAPESP, grant number 18/25010-2) for financial support and fellowships.