The New in Vivo Active Polycyclic Aromatic Derivative: 6-(1,3-dithiepan-2-yl)-2-Phenylchromane Augments Glucose Uptake in Skeletal Muscle cells and Stimulates Insulin Secretion from β-Cells by AMPK Activation

Diabetes type two (T2D) is not just very frequent metabolic disease. Recently this disease become an epidemic affecting millions of people around of globe, especially in developed countries and it becomes serious threat for the health system of entire Western civilization. Treatment of T2D and its complications draw enormous amount of human working power and government founding. Thus, the effort to create effective antidiabetic drugs is never stops. Based on our previously reported data a serial of novel polycyclic aromatic compounds were synthesized. Their effect on the rate of glucose uptake in L6 myotubes under hyperglycemic conditions was tested. Several compounds dose- and time-dependently increased the rate of glucose uptake in pharmacologically relevant concentrations. The (6-(1,3-dithiepan-2-yl)-2-phenylchromane) has showed the best glucose uptake stimulatory effect mediating by AMPK (AMP kinase) activation. Thus, this compound was also tested as potential activator of insulin secretion in INS-1E cells. Indeed, compound AMPK-dependently increased the insulin secretion in these cells. In addition, in vitro ADME parameters of the lead compound were also investigated, which showed its good drugability. Based on obtained so far data, 6-(1,3-dithiepan-2-yl)-2-phenylchromane might be used for future development of novel class of antidiabetic drugs with potential bi-functional activity: increasing both rate of glucose uptake in skeletal muscles and insulin secretion from β-cells