Isolation, crystal structure determination and cholinesterase inhibitory potential of isotalatizidine hydrate from Delphinium denudatum

Abstract

Context: Delphinium denudatum Wall (Ranunculaceae) is a rich source of diterpenoid alkaloids and is widely used for the treatment of various neurological disorders such as epilepsy, sciatica and Alzheimer’s disease.

Objective: The present study describes crystal structure determination and cholinesterase inhibitory potential of isotalatazidine hydrate isolated from the aerial part of Delphinium denudatum.

Materials and methods: Phytochemical investigation of Delphinium denudatum resulted in the isolation of isotalatazidine hydrate in crystalline form. The molecular structure of the isolated compound was established by X-ray diffraction. The structural data (bond length and angles) of the compound were calculated by Density Functional Theory (DFT) using B3LYP/6-31 + G (p) basis set. The cholinesterase inhibitory potential of the isolated natural product was determined at various concentrations (62.5, 125, 250, 500 and 1000 μg/mL) followed by molecular docking to investigate the possible inhibitory mechanism of isotalatazidine hydrate.

Results: The compound crystallized in hexagonal unit cell with space group P6_5. Some other electronic properties such as energies associated with HOMO-LUMO, band gaps, global hardness, global electrophilicity, electron affinity and ionization potential were also calculated by means of B3LYP/6-31 + G (p) basis set. The compound showed competitive type inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC₅₀ values of 12.13 μM and 21.41 μM, respectively.

Discussion and conclusion: These results suggest that isotalatazidine hydrate is a potent dual cholinesterase inhibitor and can be used as a target drug in Alzheimer diseases. This is first report indicating isotalatazidine hydrate with anticholinesterase potential.

Keywords:

• Diterpenoid alkaloid
• X-ray structure
• DFT calculations
• acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition

Acknowledgements

We are thankful to Dr. Muhammad Nisar, Chairman, Department of Botany, University of Malakand in assisting the identification of the plant.

Disclosure statement

All the authors have no financial conflict of interest.