title: Isolation, crystal structure determination and cholinesterase inhibitory potential of isotalatizidine hydrate from Delphinium denudatum.
abstract: BACKGROUND
  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.
  
  
  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 IC50values of 12.13 μM and 21.41 μM, respectively.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Chemistry , University of Malakand , Chakdara KP , Pakistan.
authors.forename: Hanif
authors.initials: H
authors.lastname: Ahmad
authors.affiliation: a Department of Chemistry , University of Malakand , Chakdara KP , Pakistan.|b Department of Pharmacy , Shaheed Benazir Bhutto University , Sheringal , KP , Pakistan.
authors.forename: Shujaat
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: a Department of Chemistry , University of Malakand , Chakdara KP , Pakistan.
authors.forename: Ezzat
authors.initials: E
authors.lastname: Khan
authors.affiliation: a Department of Chemistry , University of Malakand , Chakdara KP , Pakistan.
authors.forename: Adnan
authors.initials: A
authors.lastname: Shahzad
authors.affiliation: a Department of Chemistry , University of Malakand , Chakdara KP , Pakistan.
authors.forename: Mumtaz
authors.initials: M
authors.lastname: Ali
authors.affiliation: c Department of Physics , University of Sargodha , Sargodha , Punjab , Pakistan.
authors.forename: Muhammad Nawaz
authors.initials: MN
authors.lastname: Tahir
authors.affiliation: d HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS) University of Karachi , Karachi , Pakistan.
authors.forename: Farzana
authors.initials: F
authors.lastname: Shaheen
authors.affiliation: a Department of Chemistry , University of Malakand , Chakdara KP , Pakistan.
authors.forename: Manzoor
authors.initials: M
authors.lastname: Ahmad
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D031882:Delphinium / Q000737:chemistry*; D062105:Molecular Docking Simulation; D015394:Molecular Structure
chemical_list: D002800:Cholinesterase Inhibitors; C423465:isotalatizidine; D000157:Aconitine
keywords: DFT calculations; Diterpenoid alkaloid; X-ray structure; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition