Synthesis and Antiproliferative Effects of Amino-Modified Perillyl Alcohol Derivatives

Two series of amino-modified derivatives of (S)-perillyl alcohol were designed and synthesized using (S)-perillaldehyde as the starting material. These derivatives showed increased antiproliferative activity in human lung cancer A549 cells, human melanoma A375-S2 cells and human fibrosarcoma HT-1080 cells comparing with that of (S)-perillyl alcohol. Among these derivatives, compounds VI(5) and VI(7) were the most potent agents, with the IC(50)s below 100 μM. It was demonstrated that the antiproliferative effect of VI(5) was mediated through the induction of apoptosis in A549 cells.