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Traditionally-Used Antimalarials from the Meliaceae

[ Vol. 3 , Issue. 2 ]

Author(s):

S. Omar, J. Zhang, S. MacKinnon, D. Leaman, T. Durst, B. J.R. Philogene, J. T. Arnason, P. E. Sanchez-Vindas, L. Poveda, P. A. Tamez and J. M. Pezzuto   Pages 133 - 139 ( 7 )

Abstract:


A quantitative ethnobotanical approach to antimalarial drug discovery led to the identification of Lansium domesticum Corr. Ser. (Meliaceae) as an important antimalarial used by Kenyah Dyak healers in Indonesian Borneo. Triterpenoid lansiolides with antimalarial activity were isolated from the bark and shown to have activity in both in vitro bioassays with Plasmodium falciparum, and in mice infected with P. berghei. A survey of African and tropical American Meliaceae led to further development of the limonoid gedunin from the traditionally used medicinal plants, tropical cedar, Cedrela odorata L., and neem, Azadirachta indica A. Juss. Gedunin has significant in vitro activity but initially showed poor in vivo activity. In vivo activity was improved by (1) incorporation into an easy to absorb suspension, (2) preparation of a more stable compound, 7-methoxygedunin; and (3) synergism with dillapiol, a cytochrome P450 3A4 inhibitor. The results show the potential for both antimalarial drug and phytomedicine development from traditionally used plants.

Keywords:

Antimalarials, Meliaceae, Lansium domesticum, Plasmodium falciparum, Cedrela odorata, Azadirachta indica, 7-methoxygedunin, phytomedicine, cytochrome P450

Affiliation:

Ottawa-Carleton Institutes of Biology and Chemistry, University of Ottawa, Ottawa, ON K1N 6N5, Canada



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