Bioactivity-guided isolation of cytotoxic constituents of Brucea javanica collected in Vietnam

Brucea javanica (L.) Merr. (Simaroubaceae) is a shrub distributed from southeast Asia to northern Australia. In Asia, all parts of B. javanica have been employed as an antimalarial treatment, and the seeds of this plant have also been used for the treatment of dysentery and various skin diseases. Previous investigation on the chemical constituents of B. javanica has revealed the occurrence of apotirucallane triterpenoids, β-carboline alkaloids, and quassinoids. Quassinoids are considered the major active principles of B. javanica and have a wide spectrum of biological effects, such as potential antibabesial, anti-HIV, antimalarial, anti-tuberculosis, antitumor, cancer chemopreventive, and cytotoxic activities.

As part of an ongoing investigation on natural product anticancer agents from tropical plants and other organisms, an initial screening procedure was conducted using the MCF-7 human breast cancer cell line. A chloroform-soluble extract from the combined leaves, twigs, and inflorescence of B. javanica, collected in Vietnam, was chosen for further phytochemical study due to its high cytotoxicity. Activity-guided fractionation of this extract led to the isolation of five new triterpenoids (1-5), two known quassinoids, bruceantin (6) and bruceine A (7), and a known flavonolignan, (-)-hydnocarpin (8). Isolates 1-8 were evaluated for their cytotoxicity against three human cancer cell lines (Lu1, LNCaP, and MCF-7). The known quassinoids, bruceantin (6) and bruceine A (7), were the only cytotoxic agents obtained in this investigation, but their cytotoxic potencies of 6 and 7 for the MCF-7 cell line were increased in the presence of (-)-hydnocarpin (8).