cPtosylchloride and LiCl. Beyond four chlorinated compound was converted into the desired compound by reaction with 2 selenocoxib KSeCN in CH3CN. Synthesis selenocoxib 3 in Figure 2B. Celecoxib in the reaction TKI258 with NBS in CCl4 showed the bromine compound 5 in quantitative yield. The compound 5 was bromocelecoxib by treatment with 3 selenocoxib NaBH4 2Se2 and using ethanol as L Converted solvent with a yield of 64. 3.2. Inhibition of COX-2 enzyme by selenocoxibs Since celecoxib good inhibitor of COX-2 detected, we investigated whether the inclusion of Se in the celecoxib conditions had no effect on his fortune retardant. Characterize the kinetic mechanism of inhibition of COX-2 by celecoxib and selenocoxibs were concentration and zeitabh-Dependent kinetic parameters determined. A zeitabh-Dependent inactivation of COX-2 was observed with all three compounds. The kinact was calculated at 12.2 sec ?, 27.02 sec ? And 24.4 sec ? Celecoxib selenocoxib, 2, 3 and are selenocoxib. AI was 2.3 M, 2.4 and 0.73 for celecoxib, is calculated selenocoxib selenocoxib 2 and 3, indicating that two more potent than celecoxib and selenocoxib selenocoxib 3 was characterized by inhibition of the activity of t cyclooxygenase COX-2 . Experiments with sheep COX-1 showed no inhibition zeitabh-Dependent with these compounds. 3.3. Inhibition of proinflammatory gene expression by LPS in RAW264.7 macrophages and BMDMs selenocoxibs upregulated expression of COX-2, TNF and iNOS is stimulated classically as a biomarker of inflammation. The effect of the pretreatment of coxibs was investigated on the expression of COX-2, iNOS and TNF RAW264.
7 cells after stimulation by LPS bacterial endotoxin. A statistically significant decrease in the expression of COX-2 protein was treated only in cells selenocoxib 2 in a concentration of 0.1 M for 12 h, by LPS stimulation for 2 h, as compared to cells treated DMSOLPS observed followed. A Hnlicher Tipifarnib trend in the negative regulation of the expression of COX-2 was also selenocoxib 2 at various time points 30 min and 1 h, and start time less sp Ter seen after LPS treatment points. Selenocoxib celecoxib and 3 have entered no significant effect on COX-2 expression LPSinduced 0.1 M. A further increase increase The concentration of the inhibitor in 1 M Born in a significant inhibition of COX-2 expression with celecoxib and selenocoxib 2, w During selenocoxib 3 seems less effective. We also tested the effect of these compounds on the LPS-induced iNOS expression repealed. The dependence Dependence of the dose and inhibition of iNOS was Similar to the observed with COX-2. The results in Fig. 3A clearly showed that selenocoxib 2 decreased the expression of iNOS in a dose-dependent-Dependent manner, and more effective than celecoxib and selenocoxib 3, preferably 0.1 M. A Much the same experiment was performed in primary Ren performed macrophages derived from bone marrow of M nozzles which also ends with the results of RAW 264.7 cells. As shown in FIG. 3B selenocoxib 2 significantly inhibited LPS-induced COX-2 expression 0.1 million, compared with LPS-treated DMSO embroidered and celecoxib-treated groups, w While celecoxib and selenocoxib 3 are ineffective. However, 1 M, 2 selenocoxib celecoxib treatment then causes a significant inhibition of COX-2 expression induced by LPS, w During seems 3b selenocoxib