Synthesis and biological activities of carbonyl cobalt CORMs with selectively inhibiting cyclooxygenase-2

Abstract In this paper, three kinds of hybrid carbonyl cobalt CO-releasing molecules (CORMs), RCOOCH 2 C 2 H[Co 2 (CO) 6 ] (R = NSAIDs-COOH, 1 – 11 ; R = celecoxib derivative-COOH, 15 ), RSO 2 (R’) CH 2 C 2 H[Co 2 (CO) 6 ] (R = celecoxib, 12 ; R = nimesulide, 13 ) and ROCH 2 C 2 H[Co 2 (CO) 6 ] (R = ferulic acid etheyl ester, 14 ), were synthesized and characterized by IR, NMR and HRMS. The crystal structures of complexes 9 , 11 , 14 and 16 were determined by single-crystal X-ray diffraction. Meanwhile, the anti-tumor activity, protection on oxidative damage of H9c2 cells, anti-hypertension and myocardial protective effects were evaluated. The results showed only a part of the complexes had anticancer activity for the five cell lines compared with 5-FU. Among them, complexes 12 and 13 which modified by selective COX-2 inhibitors displayed strong antiproliferative activity and selectivity to MCF-7 cell and HT-29 cell lines, and their IC 50 values were 33.6–55.8 μM; but compared with cis-platin (DDP), they showed slightly lower activities. The complex inhibited the expression of COX-2 in HT-29 cells and MCF-7 cells, and complex 12 had stronger inhibitory effects than the others, which was accordance with its stronger activity against cell proliferation. Secondly, the complex improved the survival rate of H9c2 cells injured by H 2 O 2 . For each tested complex, the survival rate increased obviously after the cells treated with H 2 O 2 for 1h; but it increased slowly when the cells harmed for 8h due to the severe cell injury. In addition, the complexes displayed antihypertensive effects on spontaneously hypertensive rats, accompanying with good myocardium protection. This indicates these hybrid CORMs reduced myocardial toxicity of COX-2 inhibitors like, but there still has liver and kidney side-effects when administrating continuously for 14 days.