New N-functionalized benziodazoles were prepared by the peracetic oxidation of 2-iodobenzamides derived from alanine or valine. X-ray crystal structural analysis of two benziodazole-based phenyliodonium derivatives provides insight into facile interchange between benziodazoles and iminium benziodoxoles under acidic or basic conditions. [reaction: see text]

No abstract

Type 2 diabetes (T2D) is caused by loss of pancreatic b-cell mass and failure of the remaining b-cells to deliver sufficient insulin to meet demand. b-Cell glucolipotoxicity (GLT), which refers to combined, deleterious effects of elevated glucose and fatty acid levels on b-cell function and survival, contributes to T2D-associated b-cell failure. Drugs and mechanisms that protect b-cells from GLT stress could potentially improve metabolic control in patients with T2D. In a phenotypic screen seeking lowmolecular-weight compounds that protected b-cells from GLT, we identified compound A that selectively blocked GLT-induced apoptosis in rat insulinoma cells. Compound A and its optimized analogs also improved viability and function in primary rat and human islets under GLT. We discovered that compound A analogs decreased GLT-induced cytosolic calcium influx in islet cells, and all measured b-cell-protective effects correlated with this activity. Further studies revealed that the active compound from this series largely reversed GLTinduced global transcriptional changes. Our results suggest that taming cytosolic calcium overload in pancreatic islets can improve b-cell survival and function under GLT stress and thus could be an effective strategy for T2D treatment.