Microwave-Assisted Synthesis of 2(1H)-Pyridones and Their Glucosides as Cell Proliferation Inhibitors

Abstract

A new series of substituted 2(1H)-pyridones (4a–i) and their glucosides (5, 6a–e) were prepared as potential agents against leukemia (HL-60) cells. Glucosides (5,6a–e) were synthesized using three independent methods. Microwave protocol as an ecologically new method was used to synthesize the target compounds. Structures of the new products were confirmed using one- and two-dimensional NMR spectroscopy. In vitro exposure of pyridones substituted at position 4 with a 2-thienyl or 2-(trifluoromethyl)phenyl were found to exhibit high antiproliferation activities; in particular, 3-cyano-4-(thien-2′-yl)-6-(4″-chlorophenyl)-2(1H)-pyridone (4c) and its glucoside analogue (6c) had the highest activity.

Keywords:

• Microwave synthesis
• pyridone glucosides
• spectroscopy
• antiproliferation activities

Acknowledgments

The authors thank the Deanship of the Graduate Studies, M.Sc. Program (Environmental Sciences) and the Department of Chemistry, UAE University for Shaikha S. Al-Neyadi'ss M.Sc. fellowship. This work was published in ICHC-22, St. Johns’ NL, Canada, August 2009.