Abstract
The crude extract of Brucea javanica showed strong in vitro inhibitory activity against Trypanosoma evansi. Among the isolated quassinoids, bruceines A, C, and bruceantinol were found to be the most potent compounds against T. evansi. To gain a deeper understanding of the relationship between the free hydroxyl groups and the activity, several O-acetylated derivatives of bruceines A and C were synthesized and their in vitro antitrypanosomal activities against trypomastigotes of T. evansi were examined and compared with those of the original compounds. The following structure–activity relationships were observed: (1) the free hydroxyl groups at positions C-3, C-11, and C-12 are essential for antitrypanosomal activity; (2) the C-11 and C-12 hydroxyl groups are more important for the activity than the enolic hydroxyl group at C-3, and; (3) the free hydroxyl group at C-4′ of bruceine C does not have any significant effect on the activity.
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Acknowledgments
The authors are grateful to Mr. Yusuke Takata and Dr. Eri Fukushi (GC–MS and NMR Laboratory, Hokkaido University, Japan) for measuring the mass spectra. Financial support and a postdoctoral fellowship (to Ahmed Elkhateeb) from the Japan Society for the Promotion of Science are highly appreciated.
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Elkhateeb, A., Tosa, Y., Matsuura, H. et al. Antitrypanosomal activities of acetylated bruceines A and C; a structure–activity relationship study. J Nat Med 66, 233–240 (2012). https://doi.org/10.1007/s11418-011-0571-5
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DOI: https://doi.org/10.1007/s11418-011-0571-5