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

Jiaojiao Chen; Min Lu; Yongkui Jing; Jinhua Dong

doi:10.1016/j.bmc.2006.06.013

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

Bioorg Med Chem. 2006 Oct 1;14(19):6539-47. doi: 10.1016/j.bmc.2006.06.013. Epub 2006 Jun 27.

Authors

Jiaojiao Chen¹, Min Lu, Yongkui Jing, Jinhua Dong

Affiliation

¹ School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.

PMID: 16806947
DOI: 10.1016/j.bmc.2006.06.013

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / genetics
Actins / physiology
Antineoplastic Agents, Phytogenic / chemical synthesis*
Antineoplastic Agents, Phytogenic / pharmacology
Blotting, Western
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclin-Dependent Kinase Inhibitor p21 / genetics
Cyclohexane Monoterpenes
Cyclohexenes
Extracellular Signal-Regulated MAP Kinases / genetics
Extracellular Signal-Regulated MAP Kinases / physiology*
Farnesyltranstransferase / metabolism
Humans
Indicators and Reagents
Limonene
Magnetic Resonance Spectroscopy
Male
Mass Spectrometry
Mitogen-Activated Protein Kinases / physiology
Monoterpenes / chemical synthesis*
Monoterpenes / pharmacology
Prostatic Neoplasms / drug therapy*
Prostatic Neoplasms / pathology
Signal Transduction / drug effects
Signal Transduction / physiology
Structure-Activity Relationship
Terpenes / chemical synthesis*
Terpenes / pharmacology
Tetrazolium Salts
Thiazoles

Substances

Actins
Antineoplastic Agents, Phytogenic
CDKN1A protein, human
Cyclin-Dependent Kinase Inhibitor p21
Cyclohexane Monoterpenes
Cyclohexenes
Indicators and Reagents
Monoterpenes
Terpenes
Tetrazolium Salts
Thiazoles
carvone
Limonene
Farnesyltranstransferase
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinases
thiazolyl blue