Synthesis of amide and sulfonamide substituted N-aryl 6-aminoquinoxalines as PFKFB3 inhibitors with improved physicochemical properties.

In oncology, the "Warburg effect" describes the elevated production of energy by glycolysis in cancer cells. The ubiquitous and hypoxia-induced 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) plays a noteworthy role in the regulation of glycolysis by producing fructose-2,6-biphosphate (F-2,6-BP), a potent activator of the glycolysis rate-limiting phosphofructokinase PFK-1. Series of amides and sulfonamides derivatives based on a N-aryl 6-aminoquinoxaline scaffold were synthesized and tested for their inhibition of PFKFB3 in vitro in a biochemical assay as well as in HCT116 cells.

Discovery and Structure-Activity Relationships of N-Aryl 6-Aminoquinoxalines as Potent PFKFB3 Kinase Inhibitors.

Energy and biomass production in cancer cells are largely supported by aerobic glycolysis in what is called the Warburg effect. The process is regulated by key enzymes, among which phosphofructokinase PFK-2 plays a significant role by producing fructose-2,6-biphosphate; the most potent activator of the glycolysis rate-limiting step performed by phosphofructokinase PFK-1. Herein, the synthesis, biological evaluation and structure-activity relationship of novel inhibitors of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), which is the ubiquitous and hypoxia-induced isoform of PFK-2, are reported.

Modification of Polyhedral Oligomeric Silsesquioxanes (POSS) Molecules by Ruthenium Catalyzed Cross Metathesis.

The scope of ruthenium (Ru)-catalyzed cross metathesis (CM) of allyl-decorated polyhedral oligomeric silsesquioxanes (POSS) was explored. A variety of different commercial and non-commercial ruthenium complexes were tested to determine that the nitro-activated Ru catalyst is optimal for this transformation. The reported transformation was used to prepare selected hybrid steroid-POSS compounds.

Prediction of the conditions for the consumption of game by Polish consumers.

Due to the changing needs of consumers and the increased risk of diet-related diseases, today's consumers are forced to seek alternative types of meat. It should, on one hand be tasty, and on the other will improve the health of the consumer. Game is considered to be such a meat.

A fused meso-aminoporphyrin: a switchable near-IR chromophore.

An aryl amine attached to the meso position of a porphyrin controls the π-delocalization using a redox process or a protonation/deprotonation centered at the meso-nitrogen. An easily accessible modulated motif affords a switchable near-IR chromophore as reflected by significant changes in absorption and fluorescence spectra.