The synthesis of L-carvone and limonene derivatives with increased antiproliferative effect and activation of ERK pathway in prostate cancer cells

Thirty-one novel derivatives of carvone, carveol, and limonene were designed and synthesized using L-carvone as a starting material via chlorination, nucleophilic substitution, and reduction. The structures of these derivatives were characterized by MS and H-1 NMR. The antiproliferative effect was evaluated in human prostate cancer LNCaP cells. L-Carvone, L-carveol, and L-liruonene were weak cell growth inhibitors and introduction of 4-(2-methoxyphenyl)piperazine to carvone, carveol or limonene significantly increased their antiproliferative effect. The antiproliferative effect was correlated with ERK activation and p21(waf1) induction. (c) 2006 Elsevier Ltd. All rights reserved.