Hai, Yang; Geng, Jia-Jia; Li, Peng-Jie; Ma, Wei-Ping; Wang, Cui-Fang; Wei, Mei-Yan; Hou, Xue-Mei; Chen, Guang-Ying; Gu, Yu-Cheng; Liu, Ming; Shao, Chang-Lun published the artcile< Semisynthesis and biological evaluation of (+)-sclerotiorin derivatives as antitumor agents for the treatment of hepatocellular carcinoma>, Recommanded Product: 3-(Aminomethyl)-6-(trifluoromethyl)pyridine, the main research area is hepatocellular cervical carcinoma sclerotiorin antitumor cytotoxicity pharmacokinetics signaling; (+)-Sclerotiorin; AKT and ERK proteins; Antitumor; Hepatocellular carcinoma; Mouse xenograft model.
Hepatocellular carcinoma is one of the most common primary hepatic malignancy. Herein, a series of semisynthesized derivatives (2-30) of the natural product (+)-sclerotiorin (1) was prepared and evaluated the cytotoxic activities against six cancer cell lines. Among them, 3 and 5 were the most effective compounds against human hepatocellular carcinoma Bel-7402 cell line with IC50 values of 1.45 and 1.15 μM, resp. Mol. mechanism study showed that 5 disrupted the mitochondrial membrane potential and induced apoptosis in a caspase-dependent manner. In addition, 5 affected AKT and ERK signaling pathways and induced AKT and ERK proteins degradation through ubiquitin-proteasome system. Furthermore, 5 displayed significant in vivo anticancer effects in the xenograft models with decreasing the tumor mass by 52.5%. The safety evaluation was confirmed by acute toxicity subchronic toxicity tests, paraffin sections of mice organ and blood routine examination Taken together, 5 can be developed as a potential therapeutic agent for hepatocellular carcinoma.
European Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 387350-39-2 belongs to class pyridine-derivatives, and the molecular formula is C7H7F3N2, Recommanded Product: 3-(Aminomethyl)-6-(trifluoromethyl)pyridine.