Study on the biological mechanism of urolithin a on nasopharyngeal carcinoma in vitro.

CONTEXT: Urolithin A (UroA) can inhibit the growth of many human cancer cells, but it has not be reported if UroA inhibits nasopharyngeal carcinoma (NPC) cells. OBJECTIVE: To explore the inhibitory effect of UroA on NPC and potential mechanism in vitro. MATERIALS AND METHODS: RNA-sequencing-based mechanistic prediction was conducted by comparing KEGG enrichment of 40 µM UroA-treated for 24 h with untreated CNE2 cells. The untreated cells were selected as control. After NPC cells were treated with 20-60 µM UroA, proliferation, migration and invasion of were measured by colony formation, wound healing and transwell experiments. Apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) were measured by flow cytometry, Hoechst 33342, Rhodamine 123, JC-1 staining and ROS assay methods, respectively. Gene and protein expression were measured by RT-qPCR and Western blotting assay. RESULTS: RNA-sequencing and KEGG enrichment revealed UroA mainly altered the ECM receptor interaction pathway. UroA inhibited cells proliferation, epithelial-mesenchymal-transition pathway, migration and invasion with IC50 values of 34.72 µM and 44.91 µM, induced apoptosis, MMP depolarization and increase ROS content at a concentration of 40 µM. UroA up-regulated E-cadherin, Bax/Bcl-2, c-caspase-3 and PARP proteins, while inhibiting COL4A1, MMP2, MMP9, N-cadherin, Vimentin and Snail proteins at 20-60 µM. Moreover, co-treatment of UroA (40 µM) and NAC (5 mM) could reverse the effect of UroA on apoptosis-related proteins. DISCUSSION AND CONCLUSIONS: RNA-sequencing technology based on bioinformatic analyses may be applicable for studiying the mechanism of drugs for tumour treatment.

Radical-mediated divergent cyclization of benzamides toward perfluorinated or cyanated isoquinolinediones.

A simple and efficient copper-controlled divergent cyclization of benzamides, which leads to perfluorinated or cyanated isoquinolinediones, is developed. In the presence of AIBN, methacryloyl benzamides with perfluoroalkyl iodides undergo cascade radical addition/cyclization to afford perfluoroinated isoquinolinediones as the major product under metal-free conditions, whereas the use of CuI (10 mol%) is able to redirect the cyclization to yield isoquinolinediones bearing an α-cyano quaternary carbon center. The cyclization features controllable divergent synthesis and a broad substrate scope as well as highly practical reaction conditions, thereby making this strategy a highly attractive means to fluorinate or cyanate isoquinolinediones.

Synthesis of Perfluorinated Isoquinolinediones through Visible-Light-Induced Cyclization of Alkenes.

A novel visible-light-induced carboperfluoroalkylation of alkenes using perfluoroalkyl iodides and bromides as Rf sources, leading to isoquinoline-1,3-diones, was developed. This method offers rapid entry to perfluorinated isoquinoline-1,3(2H,4H)-diones from N-alkyl-N-methacryloyl benzamides under mild reaction conditions, allowing for the incorporation of a wide variety of perfluorinated groups such as CF3, C3F7, C4F9, C6F13, C8F17, C10F21, and CF2CO2Et.

Aerobic oxidative cyclization of benzamides via meta-selective C-H tert-alkylation: rapid entry to 7-alkylated isoquinolinediones.

A novel copper-catalyzed aerobic oxidative cyclization of benzamides via meta-selective C-H tert-alkylation using AIBN and analogues as radical precursors was described. This strategy provides an elusive and rapid means to 7-tert-alkylated isoquinolinediones, as well as the construction of tertiary alkyl-aryl C(sp(3))-C(sp(2)) bonds with positional selectivity.