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

Abstract

The formation of bismuth(III) complexes of carboxylates and benzoates derived from the 1 : 3 reaction of BiPh₃ 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 [BiL₃]_n, with the complexes derived from ketoprofen and sulindac having an additional single bismuth bound H₂O 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 ≥6.25 μg mL⁻¹.