Serum glucose and triglyceride lowering activity of some novel glitazones against dexamethasone-induced hyperlipidemia and insulin resistance

Objectives: To study the serum glucose and triglyceride lowering activity of some novel glitazones against dexamethasone-induced hyperlipidemia and insulin resistance in rats. Materials and Methods: Serum glucose and triglyceride lowering activity of the test compounds and a standard, rosiglitazone, was tested at a dose of 10 mg/kg p.o. against dexamethasone-induced hyperlipidemia and insulin resistance in Sprague-Dawley (SD) rats. On day 11 of treatment, blood was collected for the estimation of serum glucose and triglyceride levels. Results: All the 14 compounds and rosiglitazone significantly (P < 0.05) decreased dexamethasone-induced elevation of serum glucose when compared to dexamethasone-alone-treated group. Among these compounds, compound 10 showed better antihyperglycemic activity than rosiglitazone. Compounds 7, 8 and 9 have shown significant (P < 0.05) serum triglyceride lowering activity than did rosiglitazone. Out of the 14 compounds tested, only compounds 7, 8 and 9 have shown both serum glucose and triglyceride lowering activity. Conclusion: The present study indicates that some of the newer glitazones show significant glucose and triglyceride lowering activity. In comparison to rosiglitazone, these glitazones show comparable serum glucose lowering and better triglyceride lowering activity

A multifaceted approach for the development of novel Hantzsch 1,4-dihydropyridines as anticancer agents: Rational design, parallel synthesis, analysis, cytotoxicity and EGFR/HER2 inhibition studies

Dihydropyridines (DHPs) exhibit a wide range of pharmacological properties especially against cancer. In this context, a new series of 1,4-dihydropyridines were meticulously designed employing scaffold hybridization technique targeting the EGFR/HER2 receptors. The parallel synthesis of the designed dihydropyridines was achieved using the Hantzsch multiple component reactions. Following the synthesis, rigorous purification methods were carried out and elucidation of their chemical structures through comprehensive analytical techniques such as IR, NMR, and Mass Spectrometry. The initial synthetic step of acetoacetanilide formation was of less product yield contrasting with the satisfactory yields achieved for final multicomponent reactions. The synthesized ligands were subjected to screening against MCF-7 breast cancer and normal Vero cells to evaluate their potential anti-cancer activity. This assessment was carried out by quantifying cytotoxicity levels and structure activity relationships. Among them, compounds 6 and 14 exhibited the good inhibitory effects on the proliferation of MCF-7 cells with an IC50 value of 14.44 and 14.38 μM, respectively, which was quite closer to that of Lapatinib. Furthermore, the influence of ligands on target proteins expressions were assessed via flow cytometry experiments against EGFR &amp; HER2. Computational studies were also performed to correlate the experimental results