Tri-substituted imidazole analogues of SB203580 as inducers for cardiomyogenesis of human embryonic stem cells

• Published in: Bioorganic & medicinal chemistry letters 2013-06, Vol.23 (11), p.3300-3303
• Main Authors: Low, Joo-Leng, Jürjens, Gerrit, Seayad, Jayasree, Seow, Jasmine, Ting, Sherwin, Laco, Filip, Reuveny, Shaul, Oh, Steve, Chai, Christina L.L.
• Format: Article
• Language: English
• Subjects: Cardiomyocytes; Cell Differentiation - drug effects; cell growth; chemistry; Differentiation; embryonic stem cells; Embryonic Stem Cells - cytology; Human embryonic stem cells; Humans; Imidazoles; Imidazoles - chemistry; Imidazoles - metabolism; Imidazoles - pharmacology; mitogen-activated protein kinase; Mitogen-Activated Protein Kinase 14 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 14 - metabolism; Myocytes, Cardiac - cytology; p38 MAPK; Protein Binding; Pyridines - chemistry; Pyridines - metabolism
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.03.103

The p38α mitogen-activated protein kinase (MAPK) inhibitor SB203580 had been reported to enhance the cardiomyogenesis of human embryonic stem cells (hESCs). To investigate if tri-substituted imidazole analogues of SB203580 are equally effective inducers for cardiomyogenesis of hESCs, and if there is a correlation between p38α MAPK inhibition and cardiomyogenesis, we designed and synthesized a series of novel tri-substituted imidazoles with a range of p38α MAPK inhibitory activities. Our studies demonstrated that suitably designed analogues of SB203580 can also be inducers of cardiomyogenesis in hESCs and that cell growth is affected by changes in the imidazole structures.