Bismuth(III) complexes derived from non-steroidal anti-inflammatory drugs and their activity against Helicobacter pylori.
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).
Andrews
Philip C
PC
School of Chemistry, Monash University, PO Box 23, Clayton, Melbourne, Vic. 3800, Australia. phil.andrews@sci.monash.edu.au
Ferrero
Richard L
RL
Junk
Peter C
PC
Kumar
Ish
I
Luu
Quynh
Q
Nguyen
Kim
K
Taylor
James W
JW
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001729:Bismuth / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D004355:Drug Stability; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D007660:Ketoprofen / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D013467:Sulindac / Q000737:chemistry; D013818:Thermogravimetry
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D056831:Coordination Complexes; D013467:Sulindac; D007660:Ketoprofen; D001729:Bismuth