• African health sciences · Aug 2001

    Bioassay-guided studies on the cytotoxic and in vitro trypanocidal activities of a sesquiterpene (Muzigadial) derived from a Ugandan medicinal plant (Warburgia ugandensis).

    • D Olila, J Opuda-Asibo, and Olwa-Odyek.
    • Department of Veterinary Physiological Sciences, Makerere University, P.O. Box 7062, Kampala, Uganda. vetmuk@afsat.com
    • Afr Health Sci. 2001 Aug 1; 1 (1): 121512-5.

    AbstractTrypanosomosis is arguably the most important disease of man and his domesticated animals in the tropics. There are few compounds available for its treatment. This has exacerbated the development of drug resistance. There is therefore urgent need to search for newer compounds to treat this important disease. Medicinal plants represent a potential source of the drugs. This paper reports a bioassay-guided study to search for possible biological activity (cytotoxic and trypanocidal) in two Ugandan medicinal plants. The methodology adopted was the so-called 'ping-pong' approach, involving phytochemical purification (column chromatography and preparative thin layer chromatography), alongside biological studies (cytotoxicity, antibacterial, trypanocidal and antifungal studies). Phytochemical investigations of Zanthoxylum chalybeum (seed) yielded a pure crystalline compound, 27-135D, which was characterized by 'HNMR as the alkaloid skimmianine. Studies on stem bark yielded three alkaloids 27-165A, 27-173A and 27-173B. All the above pure isolates, and the crude extracts of Z. chalybeum had neither biological activity nor cytotoxicity in the brine shrimp assay. A cytotoxic sesquiterpine, characterized as muzigadial, was isolated from W. ugandensis. It was highly toxic in the brine shrimp assay and also had in vitro trypanocidal activity against IL 3338 as well as IL1180; reference drug-resistant and drug-sensitive trypanosome strains respectively, comparable to diminazene aceturate and Geneticin (G418). Muzigadial also had antifungal activity against Candida albicans. It was concluded that the brine shrimp assay might be a useful predictor of trypanocidal activity of plant extracts and that muzigadial may be potentially valuable in the treatment of drug-resistant trypanosomosis.

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