Aryl Ketones from Acronychia pedunculata with Cyclooxygenase-2 Inhibitory Effects

Authors

  • Wimal Pathmasiri,

    1. Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala (phone: +46-18-4714492; fax: +46-18-509101)
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  • Hesham R. El-Seedi,

    1. Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala (phone: +46-18-4714492; fax: +46-18-509101)
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    • On leave from Department of Chemistry, Faculty of Science, El-Menoufia University, El-Kom, El-Menoufia, Egypt.

  • Xiao Han,

    1. Center for Surface Biotechnology, Biomedical Centre, Uppsala University, Box 577, SE- 751 23 Uppsala
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  • Jan-Christer Janson,

    1. Center for Surface Biotechnology, Biomedical Centre, Uppsala University, Box 577, SE- 751 23 Uppsala
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  • Ulrika Huss,

    1. Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala (phone: +46-18-4714492; fax: +46-18-509101)
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  • Lars Bohlin

    1. Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala (phone: +46-18-4714492; fax: +46-18-509101)
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Abstract

1-[2,4-Dihydroxy-6-methoxy-3,5-bis(3-methylbut-2-en-1-yl)phenyl]ethanone (1), and a new aryl ketone, named acrovestenol (2), were isolated as cyclooxygenase-2 (COX-2) inhibitory principles from a CH2Cl2 extract of the bark of Acronychia pedunculata by a bioassay-guided fractionation procedure. Compound 2 inhibited COX-2 with an IC50 value of 142.0±2.15 μM, compared to the COX-2 inhibitory reference compound NS-398 with an IC50 value of 11.3±1.12 μM. Compound 1 inhibited COX-2-catalyzed PG biosynthesis with 68% at a concentration of 500 μM. The structures were determined by UV, IR, and 1D- and 2D-NMR, including TOCSY, HSQC-DEPT, and HMBC, and MS investigations.

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