Synthesis of orotic acid derivatives and their effects on stem cell proliferation

Orotic acid, a natural product, is involved in many biological processes. Human mesenchymal stem cells (hMSCs) have the potential of self-renewable and proliferation. They are commonly isolated from the bone marrow aspirates of large bones. The osteogenic potential of these stem cells has been extensively exploited by scientists in the past to evaluate the performance of synthetic scaffolds developed for tissue engineering. In this study, -arylhydrazone derivatives of orotic acid have been synthesized, and their potential as stimulators of human mesenchymal stem cells has been evaluated. Some of the analogs exhibit well to moderate effect on the proliferation rate. Orotic acid esters and several -arylhydrazones derivatives were synthesized and evaluated for their stem cell proliferation potential with human stromal stem cells (hMSCs) which was never studied before. Some of the derivatives exhibit convincing upregulation of proliferation which is believed to be due to substitution on the aromatic ring.