Research Highlights

Painkiller made smarter

doi:10.1038/nindia.2011.39 Published online 21 March 2011

Researchers have designed a new class of prodrugs from diclofenac sodium that are effective at reducing the risks of ulcer formation.

Diclofenac sodium is a non-steroidal anti-inflammatory agent that is widely used in the long-term treatment of rheumatoid arthritis. The most frequent adverse side effects of the long-term administration of diclofenac sodium are gastrointestinal disturbances, peptic ulcer and gastrointestinal bleeding.

To avoid such conditions, the researchers chose instead to design prodrugs of diclofenac sodium. Prodrugs are pharmacologically inactive compounds that can be converted to active drugs by metabolic biotransformations at specific target sites within the body.

The researchers synthesized prodrugs of diclofenac and evaluated their efficacy in both cultured and animal studies. They found that the prodrugs rapidly underwent enzymatic hydrolysis to release the parent drug diclofenac within 30–60 minutes in rat liver cells and rat blood.

The diclofenac prodrugs bound to fat molecules, despite being crystalline in nature. The researchers say that one of the prodrugs was found to be a superior candidate for the treatment of chronic inflammatory diseases such as rheumatoid arthritis.


References

  1. Bandgar, P. B. et al. Synthesis, characterization, and biological evaluation of novel diclofenac prodrugs. J. Med. Chem. 54, 1202-1210 (2011) | Article | PubMed | ISI |