Fig 1: Comparative enrichment plot for a selection against sEH. Enrichment in the target data set is plotted along the horizontal axis against the measured enrichment for a control sample, an NTC, on the vertical axis. This DEL included compounds previously assayed for sEH inhibition by Thalji et al.30 as disynthons from cycles 1 and 3. Each point in the plot is a different n-synthon from the DEL, and the points highlighted in green correspond to analogues of the two most potent of the previously reported compounds. Both of these known inhibitor structures were observed in the target data but not the NTC, and the most potent inhibitors from the earlier publication were significantly more enriched in the target data set than the weaker inhibitors. The remaining points correspond to different combinations of amino acids in cycle 1 and amines in cycles 2 and 3 of the triazine DEL.
Fig 2: Study of binding mechanism between compounds 8, 10, 12, 19 and sEH: Dixon plots for compounds 8 (A), 10 (B), 12 (C) and 19 (D), respectively. Lineweaver–Burk plots for compounds 8 (E), 10 (F), 12 (G) and 19 (H), respectively. Data are the mean of three experiments carried out in triplicate and were determined by one-way analysis of variance followed by Dunnett’s multiple comparison test, p < .05 versus control.
Fig 3: The RMSD (A), the potential energy (B), RMSF (C), and hydrogen bonds (D) of simulated interaction between sEH and inhibitor 2 calculated during 20 ns. The distance of 3? hydroxyl group of inhibitor 2 from hydroxyl group of Tyr343 (E, F).
Fig 4: Study of the binding mechanisms between compounds 1–7 and sEH: (A–G) Lineweaver-Burk plots for compounds 1–7, respectively; (a–g) Dixon plots for compounds 1–7, respectively. Data are the mean of three experiments carried out in triplicate and were determined by one-way analysis of variance, followed by Dunnett’s multiple comparison test, p < 0.05 versus control.
Fig 5: Inhibitory activity on sEH, of compounds extracted from A. americana: compounds 1–8 (A); and compounds 1, 2, and 8 (B); Lineweaver–Burk plot and Dixon plot, respectively: compound 1 (C,E) and compound 2 (D,F).
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