Discovery of novel glitazones incorporated with phenylalanine and tyrosine: Synthesis, antidiabetic activity and structure–activity relationships

We report a series of new glitazones incorporated with phenylalanine and tyrosine. All the compounds were tested for their in vitro glucose uptake activity using rat-hemidiaphragm, both in presence and absence of insulin. Six of the most active compounds from the in vitro screening were taken forward for their in vivo triglyceride and glucose lowering activity against dexamethazone induced hyperlipidemia and insulin resistance in Wistar rats. The liver samples of rats that received the most active compounds, 23 and 24, in the in vivo studies, were subjected to histopathological examination to assess their short term hepatotoxicity. The investigations on the in vitro glucose uptake, in vivo triglyceride and glucose lowering activity are described here along with the quantitative structure–activity relationships.

Illustration about synthesis, analysis and antidiabetic activity is described along with the structure–activity relationships. Compounds 23 and 24 were found to be the most active compounds.Figure optionsDownload as PowerPoint slideHighlights
► Synthesis and analysis of glitazones incorporated with phenylalanine and tyrosine.
► Screening for in vitro glucose uptake activity using rat-hemidiaphragm.
► Quantitative structure–activity relationships using CoMSIA.
► In vivo triglyceride and glucose lowering activity for the selected compounds.
► Preliminary hepatotoxicity study for the active compounds via histopathology.