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Planta Med 2015; 81(12/13): 1163-1168
DOI: 10.1055/s-0035-1546106
Natural Product Chemistry
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Cytotoxic Amides from Fruits of Kawakawa, Macropiper excelsum [*]

Authors

  • Jeremy Lei

    1   Department of Chemistry, University of Otago, Dunedin, New Zealand

  • Elaine J. Burgess

    2   The New Zealand Institute for Plant & Food Research Limited, Department of Chemistry, University of Otago, Dunedin, New Zealand

  • Alistair T. B. Richardson

    1   Department of Chemistry, University of Otago, Dunedin, New Zealand

  • Bill C. Hawkins

    1   Department of Chemistry, University of Otago, Dunedin, New Zealand

  • Sarah K. Baird

    3   Department of Pharmacology & Toxicology, University of Otago, Dunedin, New Zealand

  • Bruce M. Smallfield

    2   The New Zealand Institute for Plant & Food Research Limited, Department of Chemistry, University of Otago, Dunedin, New Zealand

  • John W. van Klink

    2   The New Zealand Institute for Plant & Food Research Limited, Department of Chemistry, University of Otago, Dunedin, New Zealand

  • Nigel B. Perry

    1   Department of Chemistry, University of Otago, Dunedin, New Zealand
    2   The New Zealand Institute for Plant & Food Research Limited, Department of Chemistry, University of Otago, Dunedin, New Zealand
Further Information

Publication History

received 12 March 2015
revised 14 April 2015

accepted 19 April 2015

Publication Date:
03 June 2015 (online)

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Abstract

Cytotoxic amides have been isolated from the fruits of the endemic New Zealand medicinal plant kawakawa, Macropiper excelsum (Piperaceae). The main amide was piperchabamide A and this is the first report of this rare compound outside the genus Piper. Eleven other amides were purified including two new compounds with the unusual 3,4-dihydro-1(2H)-pyridinyl group. The new compounds were fully characterized by 2D NMR spectroscopy, which showed a slow exchange between two rotamers about the amide bond, and they were chemically synthesized. In view of the antitumor activity of the related piperlongumine, all of these amides plus four synthetic analogs were tested for cytotoxicity. The most active was the piperine homolog piperdardine, with an IC50 of 14 µM against HT 29 colon cancer cells.

Key words

amides - Macropiper excelsum - Piperaceae - cytotoxicity - synthesis

* Dedicated to Professor Dr. Dr. h. c. mult. Adolf Nahrstedt on the occasion of his 75th birthday.


Supporting Information