The anti-inflammatory activity of dillapiole and some semisynthetic analogues

Figures & data

Figure 1.  The chemical structures of dillapiole (1) and safrole (2).

Figure 2.  Dillapiole (1) and its structural analogues.

Table 1.  Chemical shifts (¹H and ¹³C NMR) for dillapiole analogues.

Compounds	Chemical shift
	^1H (CDCl3, 300 MHz, δ = ppm, J = Hz)
	^13C (CDCl3, 75 MHz, δ = ppm):
Benzo[1,3]dioxole (3)	^1H: 5.9 (s, 2H, H-8), 6.78-6.84 (m, 4H, H-3, H-4, H-5, H-6).
	^13C: 100.62 (C8); 108.05 (C3, C6); 122.03 (C4, C5), 147.53 (C2, C1).
di-Hydrodillapiole (5)	^1H: 0.91 (t, 3H, H-12, J = 8.0); 1.54 (m, 2H, H-11, J = 8.0 and J = 7.1); 2.49 (t, 2H, H-10, J = 7.1); 3.73 (s, 3H, H-16); 3.95 (s, 3H, H-14) 5.87 (s, 2H, H-8); 6.34 (s, 1H, H-6).
	^13C: 13.86 (C12); 25.60 (C11), 33.57 (C10); 59.85 (C16); 59.91 (C14); 101.00 (C8); 105.38 (C7); 127.39 (C5); 135.54 (C2); 137.59 (C1); 144.39 (C3); 144.45 (C4).
Isodillapiole (6)	^1H: 1.86-1.89 (dd, 3H, H-12, J = 6.4 and J = 1.0); 3.75 (s, 3H, H-16); 3.88 (s, 3H, H-14); 5.91 (m, 1H, H-11, J = 15.1 and J = 6.4); 6.05-6.07 (d, 2H, H-8); 6.51-6.59 (m, 1H, H-10, J = 6.4 and J = 15.1); 6.96 (s, 1H, H-6).
	^13C: 18.81 (C12); 59.81 (C16); 60.10 (C14); 101.51 (C8); 102.76 (C6); 125.51 (C10); 126.62 (C5); 128.34 (C11); 134.56 (C2); 136.01 (C1); 141.43 (C4); 147.50 (C3).
di-Hydrosafrole (7)	^1H: 0.89-0.94 (t, 3H, H-12, J = 8.1); 1.52-1.64 (m, 2H, H-11, J = 8.1 and J = 7.0); 2.46-2.51 (t, 2H, H-10, J = 7.0); 5.89 (s, 2H, H-8); 6.66 (d, 1H, H-3, J = 7.5 and J = 1.5); 6.69 (s, 1H, H-6); 6.72 (d, 1H, H-4, J = 1.5 and J = 7.5).
	^13C: 13.70 (C12); 24.82 (C11), 37.78 (C10); 100.67 (C8); 108.0 (C3); 108.9 (C6); 121.11 (C4); 134.4 (C5), 146.1 (C2); 148.9 (C1).
Isosafrole (8)	^1H: 1.80-1.87 (dd, 3H, H-12, J = 6.4 and J = 1.0); 5.90 (m, 1H, H-11, J = 15.0 and J = 1.0); 6.02-6.6 (s, 2H, H-2); 6.25-6.31 (m, 1H, H-10, J = 15.0 and J = 6.5); 6.70-6.76 (dd, 1H, H-3, J = 7.5 and J = 1.5); 6.85-6.89 (dd, 1H, H-3, J = 7.5 and J = 1.5); 6.97 (s, 1H, H-6).
	^13C: 7.93 (C12); 100.86 (C8); 105.06 (C6); 108.64 (C3); 119.98 (C4); 124.96 (C11); 130.50 (C10); 132.03 (C5); 146.29 (C1); 147.38 (C2).

Table 2.  Anti-inflammatory activity of the compounds 1–8 in carrageenan-induced rat paw edema assay.

Compound*	Volume of edema (mL)^§
	0 min	30 min	60 min	90 min	120 min
Control	0.39 ± 0.03	0.53 ± 0.03	0.66 ± 0.04	0.84 ± 0.01	0.91 ± 0.01
1	0.32 ± 0.01(17)^¥	0.42 ± 0.01(20)	0.49 ± 0.04(25)	0.67 ± 0.02(20)	0.75 ± 0.04(17)
2	0.35 ± 0.01(10)	0.51 ± 0.01(4)	0.62 ± 0.02(6)	0.80 ± 0.03(5)	0.88 ± 0.01(5)
3	0.36 ± 0.01(7)	0.52 ± 0.01(2)	0.64 ± 0.02(3)	0.81 ± 0.03(3)	0.90 ± 0.02(1)
4	0.40 ± 0.04	0.56 ± 0.01	0.69 ± 0.02	0.90 ± 0.03	0.98 ± 0.03
5	0.32 ± 0.01(18)	0.40 ± 0.01(25)	0.43 ± 0.04(35)	0.55 ± 0.02(34)	0.70 ± 0.01(23)
6	0.36 ± 0.03(7)	0.51 ± 0.07(4)	0.64 ± 0.02(3)	0.80 ± 0.03(6)	0.89 ± 0.05(2)
7	0.35 ± 0.01(9)	0.48 ± 0.01(8)	0.60 ± 0.02(5)	0.79 ± 0.03(3)	0.90 ± 0.01(1)
8	0.37 ± 0.02(5)	0.50 ± 0.04(5)	0.63 ± 0.05(4)	0.80 ± 0.03(5)	0.89 ± 0.01(2)
Indomethacin	0.27 ± 0.05(29)	0.33 ± 0.03(37)	0.38 ± 0.03(42)	0.46 ± 0.08(45)	0.57 ± 0.06(38)

^*Dose levels: test compounds (50 mg/kg body weight), indomethacin (50 mg/kg body weight).

^§Values are expressed as mean ± SEM and analyzed by ANOVA.

^¥Values in parentheses (percentage anti-inflammatory activity).