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Synthetic cannabinoid quinones: Preparation, in vitro antiproliferative effects and in vivo prostate antitumor activity.

Eur J Med Chem.

PubMed

Wednesday 02 Oct 2013

Synthetic cannabinoid quinones: Preparation, in vitro antiproliferative effects and in vivo prostate antitumor activity.
Morales P, Vara D, Goméz-Cañas M, Zúñiga MC, Olea-Azar C, Goya P, Fernández-Ruiz J, Díaz-Laviada I, Jagerovic N.
Source

Instituto de Química Médica, CSIC, Calle Juan de la Cierva, 3, 28006 Madrid, Spain.
Abstract

Chromenopyrazolediones have been designed and synthesized as anticancer agents using the multi-biological target concept that involves quinone cytotoxicity and cannabinoid antitumor properties. In cell cytotoxicity assays, these chromenopyrazolediones have antiproliferative activity against human prostate cancer and hepatocellular carcinoma. It has been shown that the most potent, derivative 4 (PM49), inhibits prostate LNCaP cell viability (IC50 = 15 ?M) through a mechanism involving oxidative stress, PPAR? receptor and partially CB1 receptor. It acts on prostate cell growth by causing G0/G1 phase arrest and triggering apoptosis as assessed by flow cytometry measurements. In the in vivo treatment, compound 4 at 2 mg/kg, blocks the growth of LNCaP tumors and reduces the growth of PC-3 tumors generated in mice. These studies suggest that 4 is a good potential anticancer agent against hormone-sensitive prostate cancer.

http://www.ncbi.nlm.nih.gov/pubmed/24141201

 

 

 

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