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

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 μM) through a mechanism involving oxidative stress, PPARγ 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.

Keywords: Antiproliferative; Antitumor; Cannabinoid; Chromenopyrazoledione; EBNA; Electrochemistry; Epstein–Barr virus nuclear antigen; FITC; HT-29; HepG2; LNCaP; PBS; PC-3; PI; Prostate cancer; Quinone; ROS; S.D.; S.E.; TBAP; fluorescein isothiocyanate; heptoblastoma; human colon adenocarcinoma; lymph node carcinoma prostate; phosphate buffered saline; propidium iodide; prostate cancer; reactive oxygen species; standard deviation; standard error; tetrabutylammonium perchlorate.