Diruthenium(II, III) complexes of ibuprofen, aspirin, naproxen and indomethacin non-steroidal anti-inflammatory drugs: Synthesis, characterization and their effects on tumor-cell proliferation

Abstract

[Ru 2(dNSAID) 4Cl] and novel [Ru 2(dNSAID) 4(H 2O) 2]PF 6 complexes, where dNSAID = deprotonated carboxylate from the non-steroidal anti-inflammatory drugs (NSAIDs), respectively: ibuprofen, Hibp ( 1) and aspirin, Hasp ( 2); naproxen, Hnpx ( 3) and indomethacin, Hind ( 4), have been prepared and characterized by optical spectroscopic methods. All of the compounds exhibit mixed valent Ru 2(II, III) cores where metal–metal bonds are stabilized by four drug-carboxylate bridging ligands in paddlewheel type structures. The diruthenium complexes and their parent NSAIDs showed no significant effects for Hep2 human larynx or T24/83 human bladder tumor. In contrast, the coordination of Ru 2(II, III) core led to synergistic effects that increased significantly the inhibition of C6 rat glioma proliferation in relation to the organic NSAIDs naproxen and ibuprofen. The possibility that the complexes Ru 2-ibp and Ru 2-npx may exert effects (anti-angiogenic and anti-matrix metalloprotease) that are similar to those exhibited by NAMI-A opens new horizons for in vivo C6 glioma model studies.