Synthesis of compounds with antiproliferative activity as analogues of prenylated natural products existing in Brazilian propolis.

This work describes the syntheses and antitumoral properties of five prenyl compounds from which antiproliferative activities were predicted by using the TOPS-MODE approach, a computational method for drug design. The syntheses of 2-(3-methylbut-2-enyloxy)acetophenone (2), 2-hydroxy-5-(3-methylbut-2-enyl)acetophenone (3), 2-hydroxy-3-(1,1-dimethylallyl)acetophenone (4), and 5-(3-methylbut-2-enyl)-2-(3-methylbut-2-enyloxy)acetophenone (5) were realized by O-prenylation of phenolic compounds with prenyl bromide and by Claisen rearrangement, respectively. Reaction of 2-hydroxy-5-(3-methylbut-2-enyl)acetophenone 3 under Vilsmeier-Haack conditions with phosphoryl chloride and N,N-dimethylformamide yielded 6-(3-methylbut-2-enyl)chromone-3-carbaldehyde (6). The compounds were tested for their cytotoxicity toward a diverse panel of cultured human tumor cell lines. Compound 3 showed significant selective cytotoxic activity (IC(50) < 9 microg/ml).