## 2 Results and Discussion
### Inhibition of Cyclooxygenase (COX) by Mimosine and Their Dipeptides  
During screening for novel targets of mimosine, we found that cyclooxygenase (COX) was inhibited by mimosine. As shown in Table 4, mimosine inhibited COX-1 and COX-2 with IC\({}_{50}\) values of 29 and 21 \(\upmu\)M, respectively. These results indicated that mimosine inhibits COX-2 more potently than COX-1. Mimosine was also a more potent inhibitor of COX-2 than indomethacin (IC\({}_{50}\) = 28 \(\upmu\)M). [PERSON] _et al_. have reported that inhibition of gastoprotective prostaglandandins synthesis through COX-1 pathway will lead to the gastrointestinal side effects associated with NSAIDs [19]. Therefore, selective inhibition of COX-2 over COX-1 may be useful for treating inflammation and related disorders, as well as reducing gastrointestinal toxicities. Moreover, mimosine inhibits the transcription and translation of MIP-2 and MCP-1, which can induce inflammatory diseases through the recruitment of neutrophils and mononuclear cells, respectively [20]. These data, in addition to our results, suggest that mimosine may be a promising anti-inflammatory compound.  
Because mimosine inhibits cyclooxygenaseases, the effect of mimosine dipeptides on these enzymes was also explored. We found that most of the synthesized dipeptides were more potent inhibitors of COX-1 than mimosine. The IC\({}_{50}\) values of the six investigated compounds ranged 18-26 \(\upmu\)M as compared with mimosine (29 \(\upmu\)M). Mi-l-Val and Mi-l-Trp inhibited COX-2 more potently than indomethacin, with IC\({}_{50}\) values of 22 and 19 \(\upmu\)M, respectively. In both the COX-1 and COX-2 assay, Mi-l-Trp was the most potent inhibitor among the synthesized dipeptides.  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline \multirow{2}{*}{**Compound**} & \multirow{2}{*}{**Yield (mg)**} & \multicolumn{2}{c}{**IC\({}_{50}\) (\(\upmu\)M)**\#} & \multicolumn{2}{c}{**SI \#**} \\ \cline{3-5}  & & **COX-1** & **COX-2** & **COX-1/COX-2** \\ \hline Mi-l-Phe & 132.0 & nt & nt & nt \\ Mi-l-Phe & 48.5 & nt & nt & nt \\ Mi-l-Ala & 45.0 & nt & nt & nt \\ Mi-l-Ala & 79.0 & 19.1 \(\pm\) 1.0 \({}^{\text{b}}\) & 198.4 \(\pm\) 3.7 \({}^{\text{a}}\) & 0.10 \\ Mi-l-Pro & 105.5 & 17.9 \(\pm\) 2.1 \({}^{\text{b}}\) & 29.3 \(\pm\) 3.0 \({}^{\text{c}}\) & 0.75 \\ Mi-l-Pro & 43.0 & 21.0 \(\pm\) 2.0 \({}^{\text{ab}}\) & 127.5 \(\pm\) 7.7 \({}^{\text{b}}\) & 0.15 \\ Mi-l-Val & 17.0 & 24.4 \(\pm\) 1.4 \({}^{\text{ab}}\) & 21.7 \(\pm\) 2.0 \({}^{\text{c}}\) & 1.12 \\ Mi-l-Val & 25.0 & nt & nt & nt \\ Mi-l-Trp & 98.0 & 20.4 \(\pm\) 1.6 \({}^{\text{ab}}\) & 19.3 \(\pm\) 1.8 \({}^{\text{c}}\) & 0.95 \\ Mi-D-Trp & 71.5 & 26.1 \(\pm\) 1.3 \({}^{\text{ab}}\) & 27.5 \(\pm\) 2.2 \({}^{\text{c}}\) & 0.95 \\ Mimosine & & 28.8 \(\pm\) 2.3 \({}^{\text{a}}\) & 20.9 \(\pm\) 2.1 \({}^{\text{c}}\) & 1.38 \\ Indomethacin & & 6.1 \(\pm\) 0.9 \({}^{\text{c}}\) & 27.7 \(\pm\) 1.9 \({}^{\text{c}}\) & 0.22 \\ \hline \hline \end{tabular} \({}^{\text{i}}\) SI: selectivity index (COX-1 IC\({}_{50}\)/COX-2 IC\({}_{50}\)). \({}^{\text{ii}}\) Different letters in the same column indicate the existence of significant difference statistically. nt: not tested. Values represented as mean \(\pm\) SE.  
\end{table}
Table 4: IC\({}_{50}\) values of mimosine and their dipeptides for cyclooxygenase (COX) isoenzymes inhibition.