Affiliations 

  • 1 Department of Chemistry, University of Malakand, Chakdara, Dir (L) 18550, KP, Pakistan
  • 2 Department of Chemistry, University of Malakand, Chakdara, Dir (L) 18550, KP, Pakistan; Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal Dir (U), 18000 KP, Pakistan
  • 3 Faculty of Pharmacy, Universiti Teknologi MARA Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D.E., Malaysia; Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi MARA Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D.E., Malaysia
  • 4 HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Pakistan
  • 5 Department of Biochemistry, Abdul Wali Khan University Mardan, Khyber Pakhtunkhwa, Pakistan
  • 6 Department of Biotechnology, University of Science and Technology, Bannu, Khyber Pakhtunkhwa, Pakistan
  • 7 Department of Chemistry, University of Malakand, Chakdara, Dir (L) 18550, KP, Pakistan. Electronic address: manzoorhej@yahoo.com
Bioorg Chem, 2018 08;78:427-435.
PMID: 29698893 DOI: 10.1016/j.bioorg.2018.04.008

Abstract

Three new norditerpenoids alkaloids, 1β-hydroxy,14β-acetyl condelphine (1), jadwarine-A (2), jadwarine-B (3) along with two known alkaloids isotalatizidine hydrate (4) and dihydropentagynine (5) were isolated from medicinal plant Delphinium denudatum. The structures of natural products 1-5 were established on the basis of HR-EIMS, 1H and 13C NMR (1D & 2D) spectroscopic data as well as by comparison from literature data. The structures of compound 1 and 4 were also confirmed by single crystal X-ray diffraction studies. In-vitro AChE and BChE enzyme inhibitory activities of compounds 1-5 and molecular docking studies were performed to investigate the possible molecular inhibitory mechanism of the isolated natural products. Compound 2, 4 and 5 showed competitive inhibitory effects by inhibiting AChE and BChE, respectively, while 1 and 3 showed non-competitive inhibition. This work is the first report that provides a supporting evidence about the use of constituents of Delphinium denudatum in cerebral dementia and Alzheimer diseases.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.