Withanolides from Datura ceratocaula and Datura discolor and their acetylcholinesterase inhibitory activity

Fitoterapia. 2023 Oct:170:105655. doi: 10.1016/j.fitote.2023.105655. Epub 2023 Aug 17.

Abstract

The investigation of the chemical constituents of Datura ceratocaula and D. discolor allowed to isolate three new withanolides, datucerolide A (1) from the first species, and datudiscolides A (8) and B (9) from the second. In addition, seven known withanolides and five ubiquitous compounds were isolated from these plants, along with 27-O-β-d-glucopyranosyl dinnoxolide A (5), which was obtained as the tetraacetyl derivative 4. All the structures were elucidated by analyses of their spectroscopic and spectrometric data and that of dinnoxolide A (6) was confirmed by X-ray diffraction analysis. The structure 4 was assigned earlier to daturametelin G-Ac and that of 5 to datinolide B, therefore, it will be discussed whether these assignments are correct. On the other hand, the structure of datudiscolide A (8) was previously assigned to the aglycone of dinoxin B (14), however, a revision of its reported NMR data showed inconsistencies with the proposed structure. The inhibitory activity of withanolides 2, 3, 6-8, 12, and 13 against acetylcholinesterase enzyme (AChE) was evaluated. Compounds 6, 7, 12, and 13 exhibited the best activity with IC50 values ranging from 2.8 to 21.5 μM.

Keywords: Acetylcholinesterase inhibitors; Datura ceratocaula; Datura discolor; Solanaceae; Withanolides.

MeSH terms

  • Acetylcholinesterase
  • Datura* / chemistry
  • Molecular Structure
  • Withanolides* / chemistry
  • Withanolides* / pharmacology

Substances

  • Withanolides
  • Acetylcholinesterase