Synthesis and characterization of a diruthenium(II,III)–ketoprofen compound and study of the in vitro effects on CRC cells in comparison to the naproxen and ibuprofen derivatives

A new diruthenium(II,III) complex, of formula [Ru2Cl(ket)4], Ruket, containing the non-steroidal anti-inflammatory drug ketoprofen was synthesized and mainly characterized by electrospray ionization mass spectrometry (ESI-MS), UV–Vis–IR electronic spectroscopy and FTIR and Raman vibrational spectroscopies. The four drug-carboxylato bridging ligands stabilize a Ru2(II,III) mixed valent core in a paddlewheel type structure as confirmed by ESI mass spectra, electronic and vibrational spectroscopies and magnetic measurements. Ruket and the analogous compounds containing ibuprofen, Ruibp, and naproxen, Runpx, were tested for the biological effects in the human colon carcinoma cells HT-29 and Caco-2 expressing high and low levels of COX-2 respectively. All compounds only weakly affected the proliferation of the colorectal cancer cells HT-29 and Caco-2, and similarly only partially inhibited the production/activity of MMP-2 and MMP-9 by HT-29 cells, suggesting that COX-2 inhibition by these drugs can only partially be involved in the pharmacological effects of these derivatives.

A novel diruthenium(II,III)–ketoprofen metallodrug has been synthesized and mainly characterized by electrospray ionization mass spectrometry (ESI-MS), UV–Vis–IR electronic and FTIR and Raman vibrational spectroscopies. Ruket and the analogues containing ibuprofen, Ruibp, and naproxen, Runpx, show a mild anti-proliferative activity on the colorectal cancer cells HT-29 and Caco-2. Ruibp and Runpx are slightly more active on the Caco-2 cells that express lower levels of COX-2. The metallodrugs are able of inhibiting the production/activity of MMP-2 and MMP-9 of HT-29 cells.Figure optionsDownload as PowerPoint slideHighlights
► A diruthenium(II,III)–ketoprofen metallodrug was synthesized and characterized.
► Ru–NSAIDs were tested for biological effects in HT-29 and Caco-2 cells.
► Ru–NSAIDs showed mild anti-proliferative activity on cancer cells HT-29 and Caco-2.
► The metallodrugs inhibited production/activity of MMP-2 and MMP-9 of HT-29 cells.