Anderson, Margaret Marie; (1992) Cytotoxic and antimalarial natural products. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Eighty percent of the world's peculation must rely on traditional medicine for the treatment of disease. In a report in 1978, the World Health Organisation, recognizing that modem medicine cannot meet its aim to make healthcare available to everyone by the year 2000, has recommended the improvement and use of herbal medicine. This study focuses initially on a herbal remedy used traditionally in Chinese Medicine for the treatment of malaria. An aqueous infusion or "lea" was prepared from the fruits of the Smiaroubaceae species Brucea javanica, and four quassinoids, bruceines A, B, C, and brusatol have been isolated and identified by the use of chromatographic and spectroscopic techniques. The aqueous tea, together with crude extracts of two other related plant species, Simarouba amara and Simarouba glauca have been tested against Plasmodium falciparum in vitro, and Plasmodium berghei in vivo. The development of a microdilution assay for the assessment of cytotoxicity against KB cells, a human epidermoid nasopharyngeal carcinoma cell line, is described. The test was used to evaluate the cytotoxic activity of crude plant extracts and isolated pure compounds, shown lo demonstrate antiplasmodial activity. Some 107 compounds and crude extracts, including 21 quassinoids, 12 semi- synthetic quassinoids, 46 isoquinoline alkaloids, 4 canthin-6-one alkaloids, several known cytotoxic and therapeutic agents, and a number of natural products have been tested in the in vitro KB cytotoxicity assay. Comparisons of their antiplasmodial and cytotoxic activities are made. The effect of three patent antiplasmodial quassinoids, bruceantin, brusatol, and bruceine D, on protein and nucleic acid synthesis in KB cells has been investigated. Transmission electron microscopy has been used to demonstrate visually the effect of the same three quassinoids on cellular morphology and on the membrane surface of KB cells grown in a monolayer.

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