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 1H NMR. The antiproliferative effect was evaluated in human prostate cancer LNCaP cells. L-carvone, L-carveol, and L-limonene 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.
Chen
Jiaojiao
J
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Lu
Min
M
Jing
Yongkui
Y
Dong
Jinhua
J
D000199:Actins / Q000235:genetics / Q000502:physiology; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000502:physiology*; D051231:Farnesyltranstransferase / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D000077222:Limonene; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D039821:Monoterpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles
D000199:Actins; D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes; D007202:Indicators and Reagents; D039821:Monoterpenes; D013729:Terpenes; D013778:Tetrazolium Salts; D013844:Thiazoles; C006923:carvone; D000077222:Limonene; D051231:Farnesyltranstransferase; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; C022616:thiazolyl blue