Wang, Xiaomei; Qian, Jianqiang; Zhu, Peng; Hua, Rong; Liu, Ji; Hang, Jiaying; Meng, Chi; Shan, Wenpei; Miao, Jiefei; Ling, Yong published the artcile< Novel Phenylmethylenecyclohexenone Derivatives as Potent TrxR Inhibitors Display High Antiproliferative Activity and Induce ROS, Apoptosis, and DNA Damage>, Related Products of 6482-24-2, the main research area is Phenylmethylenecyclohexenone derivative TrxR inhibitor ROS antiproliferative DNA damage anticancer; Antiproliferative activities; Aqueous solubility; DNA damage; Phenylmethylenecyclohexenone; Reactive oxygen species; Thioredoxin reductase.
The natural product piperlonguminine (PL) has been shown to exert potential anticancer activity against several types of cancer via elevation of reactive oxidative species (ROS). However, the application of PL has been limited due to its poor water solubility and moderate activity. To improve PL′s potency, we designed and synthesized a series of 17 novel phenylmethylenecyclohexenone derivatives and evaluated their pharmacol. properties. Most of them exerted antiproliferative activities against four cancer cell lines with IC50 values lower than PL. Among these, compound 10 e not only showed good water solubility and exerted the most potent antiproliferative activity against HGC27 cells (IC50=0.76 μM), which was 10-fold lower than PL (IC50=7.53 μM), but also exhibited lower cytotoxicity in human normal gastric epithelial cells GES-1 compared with HGC27 cells. Mechanistically, compound 10 e inhibited thioredoxin reductase (TrxR) activity, increased ROS levels, and diminished mitochondrial transmembrane potential (MTP) in HGC27 cells. Furthermore, 10 e also induced G2/M cell-cycle arrest, and triggered cancer cell apoptosis through the regulation of apoptotic proteins. Finally, 10 e promoted DNA damage in HGC27 cells via the activation of the H2AX(S139ph) and p53 signaling. In conclusion, 10 e, with prominent tumor selectivity and water solubility, could be a promising candidate for the treatment of cancer and, as such, warrants further investigation.
ChemMedChem published new progress about Antiproliferative agents. 6482-24-2 belongs to class ethers-buliding-blocks, and the molecular formula is C3H7BrO, Related Products of 6482-24-2.
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem