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

Eur J Med Chem. 2015 May 5:95:552-62. doi: 10.1016/j.ejmech.2015.03.062. Epub 2015 Mar 28.

Abstract

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 μM. 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.

Keywords: Antiproliferative activity; Fatty acids; Glioma cell; Monastrol; Oil chemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemistry Techniques, Synthetic
  • Drug Design
  • Fatty Acids / chemical synthesis*
  • Fatty Acids / chemistry
  • Fatty Acids / pharmacology*
  • Glioma / pathology*
  • Humans
  • Male
  • Rats
  • Rats, Wistar
  • Uridine / analogs & derivatives*
  • Uridine / chemistry

Substances

  • Antineoplastic Agents
  • Fatty Acids
  • 5,6-dihydrouridine
  • Uridine