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A new quassinoid, yadanziolide S (1), was isolated from the seeds of the traditional Chinese medicinal herb, Brucea javanica, along with ten known compounds, flazin, bruceine D, yadanziolide B, bruceoside A, yadanziolide S, yadanzigan, glycerol 1,3-bisoleate, azelaic acid, (+/-)-8-hydroxyhexadecanoic acid, and vanillin. Compound 1 is the first quassinoid to have been isolated from B. javanica without a methyleneoxy bridge between C-8 and C-13, and its structure was determined using spectroscopic methods, and confirmed by single-crystal X-ray diffraction. All isolates were evaluated for their potential to induce human promyelocytic leukemia (HL-60) cell differentiation, and to inhibit cyclooxygenase-1 (COX-1), -2 (COX-2), and 7,12-dimethylbenz[a]anthracene (DMBA)-induced lesions in a mouse mammary organ culture model.

A microdilution technique was developed for the assessment of in vitro cytotoxicity against KB cells derived from a human epidermoid carcinoma of the nasopharynx. The test was used to determine the cytotoxicity of a series of quassinoids, isolated from Brucea javanica, and which have previously been shown to demonstrate activity against Plasmodium falciparum. The 50% effective dose (ED50) for 7 quassinoids tested against KB ranged from 0.008 microgram/ml for bruceantin, the most cytotoxic of the compounds tested to greater than 5 micrograms/ml for bruceolide, the least toxic tested. The activities of the quassinoids against KB did not parallel the known activities of the quassinoids against Plasmodium falciparum suggesting that the quassinoid mode of antimalarial action is not a simple cytotoxic effect and lends support to further investigation of the structure activity relationships within this group of compounds.

The medicinal plant, BRUCEA JAVANICA (L.) Merr. (Simaroubaceae) was examined for antimalarial properties. Among different crude solvent extracts of the fruit, the chloroform extract was shown to have the most potent IN VITRO antimalarial activity. Three active compounds were isolated and purified from the chloroform extract. These compounds were confirmed as bruceine A, bruceine B hydrate and bruceine C by UV, IR, NMR and mass spectra. When tested IN VITRO against multi-drug resistant isolates of P. FALCIPARUM bruceine A and bruceine B hydrate were similar in activity (ID50 of 8.66 and 8.15 ng/ml) whereas bruceine C had an ID50 of 1.95 ng/ml. These compounds were comparable in IN VITRO activity to the new antimalarial drug, mefloquine (ID50 of 6.26 ng/ml).

An IN VITRO antimalarial test, utilising the inhibition of uptake of [G- (3)H]-hypoxanthine into PLASMODIUM FALCIPARUM cultured in human blood, has been used to assess the activity of crude extracts of ARTEMISIA ANNUA and A. VULGARIS (Compositae) and of BRUCEA JAVANICA, AILANTHUS ALTISSIMA, and SIMABA CEDRON (Simaroubaceae).

Inhibition of the uptake of 3 H-thymidine into TLX-5 mouse lymphoma cells has been used to assess the cytotoxicity of extracts and fractions of BRUCEA JAVANICA. Six bruceolides, two dehydrobruceolides and a dihydrobruceolide have been isolated from roots, fruits and stems. Bruceine A was the major bruceolide of the roots and of the fruits. The potent antineoplastic bruceolides, bruceantin and bruceantinol, previously isolated from B. ANTIDYSENTERICA and B. GUINEENSIS have been isolated together with the novel compounds dehydrobruceine A and dihydrobruceine A. Bruceantarin and dehydrobruceine B, not previously reported from this species, and bruceines B and C were also isolated. The identification of these nine compounds by means of their UV, EIMS, CIMS, FDMS and 1 H NMR spectra is discussed.