Efficient approach to acyloxymethyl esters of nalidixic acid and in vitro evaluation as intra-ocular prodrugs

Bioorg Med Chem. 2006 Apr 15;14(8):2569-80. doi: 10.1016/j.bmc.2005.11.063. Epub 2006 Jan 18.

Abstract

Various alkylcarbonyloxymethyl esters of nalidixic acid ranging from 3 to 15 carbon units in the pro-moiety have been prepared and assessed as potential prodrugs. Their chromatographic retention factors k', silicone oil solubilities and in vitro conversion to nalidixic acid by a commercial esterase were determined together with their in vitro antimicrobial activity and cytotoxicity. The preliminary results suggest that silicone oil may have potential for the intra-ocular delivery of antibacterial compounds. Moreover, the in vitro release rate can be controlled by the lipophilicity of the prodrug.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Drug Administration Routes
  • Esters / chemistry*
  • Eye
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Microbial Sensitivity Tests
  • Nalidixic Acid / administration & dosage
  • Nalidixic Acid / chemistry*
  • Nalidixic Acid / pharmacology*
  • Prodrugs
  • Silicone Oils / chemistry
  • Solubility

Substances

  • Anti-Bacterial Agents
  • Esters
  • Prodrugs
  • Silicone Oils
  • Nalidixic Acid