New natural cholinesterase inhibiting and calcium channel blocking quinoline alkaloids

Atta Ur Rahman, Asaad Khalid, Nighat Sultana, M. Nabeel Ghayur, Osman Mesaik Mohammed Ahmed Hassan, M. Riaz Khan, Anwar H. Gilani, M. Iqbal Choudhary

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

During this study, one new coumarin; 7-O-β-D-glucopyranoside-2H-1-benzopyran-2-one (1) and three quinoline alkaloids; 3-hydroxy, 2, 2, 6-trimethyl-3, 4, 5, 6-tetrahydro-2H-pyrano[3,2-c] quinoline 5-one (2), ribalinine (3) and methyl isoplatydesmine (4) were isolated from the aerial parts of Skimmia laureola and their structures established by spectroscopic studies. Compounds 2-4 were found to be linear mixed type inhibitors of acetylcholinesterase (Ki = 110.0, 30.0 and 30.0 μM, respectively). Compounds 2 and 3 were also found to be linear mixed type inhibitors of butyrylcholinesterase, while compound 4 was a noncompetitive inhibitor of the enzyme (Ki = 90.0, 70.0 and 19.0 μM, respectively). The inhibition of acetyl- and butyryl-cholinesterase enzymes persists as the most promising therapeutic strategy for activating the impaired cholinergic functions in Alzheimer's disease and related dementias. Compound 4 also showed dose-dependent spasmolytic activity in the isolated rabbit jejunum intestinal preparation by relaxing the spontaneous (EC50 = 0.1 mg/mL) and K+-induced contractions (EC50 = 0.4 mg/mL), suggesting that the spasmolytic effect of compound 4 is mediated through the blockade of voltage-dependent Ca2+ channels.

Original languageEnglish
Pages (from-to)703-710
Number of pages8
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume21
Issue number6
DOIs
Publication statusPublished - Dec 2006
Externally publishedYes

Fingerprint

Parasympatholytics
Cholinesterases
Calcium Channels
Alkaloids
Butyrylcholinesterase
Coumarins
Cholinesterase Inhibitors
Enzyme Inhibitors
Jejunum
Cholinergic Agents
Dementia
Alzheimer Disease
Antennas
Rabbits
Electric potential
Enzymes
quinoline
Therapeutics
Inhibition (Psychology)
isoplatydesmine

Keywords

  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Calcium channel blocker
  • Enzyme inhibition
  • Quinoline alkaloids
  • Skimmia laureola

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Rahman, A. U., Khalid, A., Sultana, N., Nabeel Ghayur, M., Mohammed Ahmed Hassan, O. M., Riaz Khan, M., ... Iqbal Choudhary, M. (2006). New natural cholinesterase inhibiting and calcium channel blocking quinoline alkaloids. Journal of Enzyme Inhibition and Medicinal Chemistry, 21(6), 703-710. https://doi.org/10.1080/14756360600889708

New natural cholinesterase inhibiting and calcium channel blocking quinoline alkaloids. / Rahman, Atta Ur; Khalid, Asaad; Sultana, Nighat; Nabeel Ghayur, M.; Mohammed Ahmed Hassan, Osman Mesaik; Riaz Khan, M.; Gilani, Anwar H.; Iqbal Choudhary, M.

In: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 21, No. 6, 12.2006, p. 703-710.

Research output: Contribution to journalArticle

Rahman, AU, Khalid, A, Sultana, N, Nabeel Ghayur, M, Mohammed Ahmed Hassan, OM, Riaz Khan, M, Gilani, AH & Iqbal Choudhary, M 2006, 'New natural cholinesterase inhibiting and calcium channel blocking quinoline alkaloids', Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 21, no. 6, pp. 703-710. https://doi.org/10.1080/14756360600889708
Rahman AU, Khalid A, Sultana N, Nabeel Ghayur M, Mohammed Ahmed Hassan OM, Riaz Khan M et al. New natural cholinesterase inhibiting and calcium channel blocking quinoline alkaloids. Journal of Enzyme Inhibition and Medicinal Chemistry. 2006 Dec;21(6):703-710. https://doi.org/10.1080/14756360600889708
Rahman, Atta Ur ; Khalid, Asaad ; Sultana, Nighat ; Nabeel Ghayur, M. ; Mohammed Ahmed Hassan, Osman Mesaik ; Riaz Khan, M. ; Gilani, Anwar H. ; Iqbal Choudhary, M. / New natural cholinesterase inhibiting and calcium channel blocking quinoline alkaloids. In: Journal of Enzyme Inhibition and Medicinal Chemistry. 2006 ; Vol. 21, No. 6. pp. 703-710.
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