Strategies for improving the water solubility of new antitumour nitronaphthylbutadiene derivatives

Org Biomol Chem. 2010 Dec 21;8(24):5674-81. doi: 10.1039/c0ob00493f. Epub 2010 Oct 11.

Abstract

Different nitronaphthylbutadienes have been previously proved to have antitumour activity. The main drawback of these derivatives is their low water solubility. With the aim of facilitating the administration of these new drugs we have synthesized the hexyl (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate analogue (1-Naph-NHCB) which is demonstrated to be easily included into cyclodextrins and/or entrapped into liposomes. Its antitumour activity was revealed to be almost comparable with that of the previously studied methyl analogue ester (1-Naph-NMCB). On the other hand, in vitro studies with different cancer cell lines showed that the cytotoxic activity of both 1-Naph-NMCB and 1-Naph-NHCB were fully preserved and in some cases also enhanced when entrapped into liposomal carriers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Butadienes / chemistry*
  • Butadienes / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Molecular Structure
  • Nitro Compounds / chemistry*
  • Nitro Compounds / pharmacology
  • Solubility
  • Water / chemistry*

Substances

  • Antineoplastic Agents
  • Butadienes
  • Nitro Compounds
  • Water