New Cholinesterase-Inhibiting Triterpenoid Alkaloids from Buxus hyrcana

Authors

  • M. Iqbal Choudhary,

    1. H. E. J. Research Institute of Chemistry, International Center for Chemical Sciences, , University of Karachi, Karachi-75270, Pakistan (fax: +92-21-4819018)
    2. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical Sciences, University of Karachi, Karachi-75270, Pakistan
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  • Salma Shahnaz,

    1. H. E. J. Research Institute of Chemistry, International Center for Chemical Sciences, , University of Karachi, Karachi-75270, Pakistan (fax: +92-21-4819018)
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  • Shehnaz Parveen,

    1. H. E. J. Research Institute of Chemistry, International Center for Chemical Sciences, , University of Karachi, Karachi-75270, Pakistan (fax: +92-21-4819018)
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  • Asaad Khalid,

    1. H. E. J. Research Institute of Chemistry, International Center for Chemical Sciences, , University of Karachi, Karachi-75270, Pakistan (fax: +92-21-4819018)
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  • M. Ahmed Mesaik,

    1. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical Sciences, University of Karachi, Karachi-75270, Pakistan
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  • S. Abdul Majeed Ayatollahi,

    1. School of Pharmacy, Shaheed Beheshti University of Medical Sciences, P.O. Box 14155-61-53, Tehran, Iran
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  • Atta-ur-Rahman

    1. H. E. J. Research Institute of Chemistry, International Center for Chemical Sciences, , University of Karachi, Karachi-75270, Pakistan (fax: +92-21-4819018)
    2. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical Sciences, University of Karachi, Karachi-75270, Pakistan
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Abstract

The current phytochemical investigation on Buxus hyrcanaPojark. has resulted in the isolation of the triterpenoid alkaloids 110. The structures of five new alkaloids, hyrcanone (1), hyrcanol (2), hyrcatrienine (3), Nb-dimethylcycloxobuxoviricine (4), and hyrcamine (5), were elucidated by means of modern spectroscopic techniques, while the known alkaloids, buxidin (6), buxandrine (7), buxabenzacinine (8), buxippine-K (9) and E-buxenone (10), were identified by comparing their spectral data with those reported earlier. Compounds 1 and 39 were found to be acetyl- and butyrylcholinesterase inhibitors. The IC50 values were estimated to be in the range of 83.0–468.0 μM against AChE and 1.12–350.0  μM against BChE. The structure–activity relationship studies suggested that the presence of dimethylamino moieties at C(3) and C(20) is the most important factor influencing the activity of these compounds against the cholinesterase enzymes. All compounds were also evaluated for cytotoxicity on a fibroblast cell line with incubation of 24 h. No cytotoxic effects were exerted by any compound.

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