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

• Main Authors: Hanif Ahmad, Shujaat Ahmad, Ezzat Khan, Adnan Shahzad, Mumtaz Ali, Muhammad Nawaz Tahir, Farzana Shaheen, Manzoor Ahmad
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2017-01-01
• Series: Pharmaceutical Biology
• Subjects: diterpenoid alkaloid; x-ray structure; dft calculations; acetylcholinesterase (ache) and butyrylcholinesterase (bche) inhibition
• Online Access: http://dx.doi.org/10.1080/13880209.2016.1240207
• ISSN: 1388-0209; 1744-5116

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 P65. 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.