Bismuth(III) complexes derived from non-steroidal anti-inflammatory drugs and their activity against Helicobacter pylori

Dalton Trans. 2010 Mar 21;39(11):2861-8. doi: 10.1039/c000164c. Epub 2010 Feb 5.

Abstract

The formation of bismuth(III) complexes of carboxylates and benzoates derived from the 1 : 3 reaction of BiPh(3) with the common non-steroidal anti-inflammatory drugs (NSAIDs) ketoprofen, naproxen, ibuprofen, mefenamic acid, diflunisal, 5-chlorosalicylic acid, fenbufen, sulindac, tolfenamic acid and flufenamic acid, has been achieved using both solvent-free and solvent-mediated methods. The thermochemical profiles of the solvent-free reactions were studied using DSC-TGA. All reactions produced the tris-substituted complexes of general formula [BiL(3)](n), with the complexes derived from ketoprofen and sulindac having an additional single bismuth bound H(2)O molecule in the inner coordination sphere. The complexes are stable in air over a period of six months, do not undergo significant decomposition when suspended overnight in water, but decompose in 1 M HCl solution to release the free acid form of the NSAID. All ten complexes show excellent in vitro activity against Helicobacter pylori with MIC values of > or = 6.25 microg mL(-1).

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Bismuth / chemistry*
  • Calorimetry, Differential Scanning
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry*
  • Coordination Complexes / therapeutic use
  • Drug Stability
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori*
  • Ketoprofen / chemistry
  • Microbial Sensitivity Tests
  • Sulindac / chemistry
  • Thermogravimetry

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Coordination Complexes
  • Sulindac
  • Ketoprofen
  • Bismuth