Novel hybrid DHPM-fatty acids: Synthesis and activity against glioma cell growth in vitro

作者：Treptow Tamara G M; Figueiro Fabricio; Jandrey Elisa H F; Battastini Ana M O; Salbego Christianne G; Hoppe Juliana B; Taborda Priscila S; Rosa Sabrina B; Piovesan Luciana A; Montes D'Oca Caroline Da R; Russowsky Dennis; Montes D'Oca Marcelo G^*

来源：European Journal of Medicinal Chemistry, 2015, 95: 552-562.

DOI：10.1016/j.ejmech.2015.03.062

• Fatty acids
• Oil chemistry
• Glioma cell
• Antiproliferative activity
• Monastrol

We described the first synthesis of fatty acid 3,4-dihydropyrimidinones (DHPM-fatty acids) using the Biginelli multicomponent reaction. Antiproliferative activity on two glioma cell lines (C6 rat and U-138-MG human) was also reported. The novel DHPM-fatty acids reduced glioma cell viability relative to temozolomide. Hybrid oxo-monastrol-palmitic acid was the most potent, reducing U-138-MG human cell viability by ca. 50% at 10 mu M. In addition, the DHPM-fatty acids showed a large safety range to neural cells, represented by the organotypic hippocampal culture. These results suggest that the increased lipophilicity of DHPM-fatty acids offer a promising approach to overcoming resistance to chemotherapy and may play an important role in the development of new antitumor drugs.

• 出版日期2015-5-5