Synthesis and cytotoxic activity of isocembrol and its hydroxy derivatives

The synthesis of 2- and 3-hydroxy derivatives of isocembrol was accomplished by the epoxidation of isocembrol with tert -butyl hydroperoxide in the presence of a catalytic amount of VO(acac) 2 followed by the epoxide ring opening in the presence of LiAlH 4 . The 13-hydroxy derivative of isocembrol was synthesized by the allylic oxidation in the SeO 2 -Bu t OOH system. Using the PASS software, the 13-hydroxy derivative was predicted to be the most effective cytotoxic agent, which was esterified to form N-methylurocanate. Isocembrol exhibited the highest in vitro antitumor activity against the LOX IMVI (melanoma) and UO-31 (renal cancer) cells, causing up to 25.77 and 75.65% cell death, respectively. N-Methylurocanate led to the death of up to 51.04% UO-31 cells (renal cancer).