Inhibition of soluble epoxide hydrolase activity by compounds isolated from the aerial parts of Glycosmis stenocarpa

Figures & data

Table 1. ¹H and ¹³C NMR data for compound 11.

Position	δH*^,†	δC*^,‡
1		35.8
2α	2.21 (1H, d, J = 16.2 Hz)	53.2
2β	2.15 (1H, d, J = 16.2 Hz)
3		201.4
4	5.79 (1H, s)	122.2
5		158.5
6		45.6
7α	1.95 (1H, m)	22.0
7β	1.33 (1H, m)
8α	2.33 (1H, m)	26.5
8β	2.07 (1H, m)
9		153.9
10	4.14 (2H, s)	64.3
11	0.90 (3H, s)	18.8
12	1.13 (3H, s)	27.5
13	6.32 (1H, s)	121.9

*Measured in CD₃OD.

†600 MHz.

‡150 MHz.

Figure 1. Effects of extract on sEH inhibitory activity determined using the fluorometric method. (1) Methanol extract, (2) n-Hexane extract, (3) Chloroform extract, (4) Ethyl acetate extract and (5) Water extract.

Figure 2. Structures of compounds 1–12 from the aerial parts of G. stenocarpa.

Figure 3. Key HMBC (→) correlations of compound 11.

Table 2. The sEH inhibitory activity of compounds 1–12.

Activity of compounds on sEH*
Compound	100 µM (%)	IC50 (µM)
1	4.7 ± 1.7	N.T‡
2	86.0 ± 0.8	22.5 ± 1.7
3	98.9 ± 0.7	7.7 ± 1.2
4	42.1 ± 5.7	N.T‡
5	80.0 ± 3.5	30.0 ± 1.9
6	65.1 ± 0.0	61.5 ± 3.4
7	76.6 ± 0.4	59.5 ± 1.2
8	18.2 ± 0.0	N.T‡
9	44.3 ± 2.6	N.T‡
10	21.6 ± 0.9	N.T‡
11	13.5 ± 1.5	N.T‡
12	13.7 ± 0.9	N.T‡
AUDA (25 nM)†	58.9 ± 5.1	12.2 ± 4.1 nM

*Tested compounds were tested in a set of experiments repeated 3 times.

†Positive control.

‡N.T (not tested).

Figure 4. Lineweaver–Burk plots were constructed for the inhibition of sEH by compounds 2 (A) and 3 (B). Inserts (I) and (II) represent the secondary plot of the slope and the intercept of compounds (2 and 3).

Table 3. In vitro sEH kinetic study of compounds.

Compound*	Binding mode	Kic (µM)†	Kiu (µM)‡
2	Mixed	4.7	16.9
3	Mixed	1.0	7.0

*All the compounds were examined in a set of experiments repeated 3 times.

†Values of inhibition constant.

‡Values of enzyme–substrate complex constant.