Bioassay-directed fractionation led to the isolation of seven compounds from a sample of the dried leaves. twigs, and branches of Diospyros quaesita THW. (Ebenaceae). One of the isolates, betulinic acid 3-caffeate (1). showed in vitro antimalarial activity against Plasmodium falciparum clones D(6) (chloroquine-sensitive) and W(2) (chloroquine-resistant) with IC(50) values of 1.40 and 0.98 mu M, respectively. Evaluation of compound 1 in the human oral epidermoid (KB) cancer cell line revealed cytotoxicity at ED(50) of 4.0 mu M In an attempt to reduce the cytotoxicity of 1, the acetylated derivative la and betulinic acid (1b) were prepared. Of the seven isolates, diospyrosin (2) was determined to be a new neolignan. In addition to 1. other known compounds isolated in this study were pinoresinol, lariciresinol. N-benzoyl-L-phenylalaninol, scopoletin, and poriferast-5-en-3 beta,7 alpha-diol. The structure of 2 was elucidated based on spectroscopic data analysis including 1D- and 2D-NMR. and HR-ESI-MS.