Synthesis and biological evaluation of isoxazole molecules able to induce stem cell differentiation.

摘要

Within the past few years there has been a growing interest in the ability to use small molecules to induce stem cell differentiation and promote the production of specific cell types such as neurons and cardiomyocytes. This area of research has great potential for treating diseases and traumas such as neurological disorders, limb amputations, spinal cord injuries, burns, heart disease and diabetes. Here we describe, the identification, synthetic optimization, and biological evaluation of 3,5-disubstituted isoxazoles able to induce stem cell differentiation towards a cardiogenic and neurogenic cell fate. This dissertation outlines an extensive structure activity relationship study of these 3,5-disubstituted isoxazoles in the attempt to increase their biological activity. We also demonstrate the application of these molecules as probes in delineating the biological processes involved in stem cell differentiation with particular interest in neurogenic tumorgenesis and myocardial repair.