Neuroprotective effects of (E)-3,4-diacetoxystyryl sulfone and sulfoxide derivatives in vitro models of Parkinson's disease

Figures & data

Figure 1. The structure of (E)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides.

Table 1. Physical and analytical data for target compounds.

Compound number	n	R	Molecular formula	Molecular weight	Yield %	m.p. (°C)
1	1	H	C19H18O6S	374.1	94	163–164
2	2	H	C20H20O6S	388.1	96	99–100
3	3	H	C21H22O6S	402.1	92	76–77
4	4	H	C22H24O6S	416.1	93	79–80
5	1	Cl	C19H17ClO6S	408.1	91	136–137
6	1	t-Bu	C23H26O6S	430.2	90	146–147
7	1	CF3	C20H17F3O6S	442.1	92	134–135
8	1	OCH3	C20H20O7S	404.1	95	101–102
9	1	H	C19H18O5S	358.1	90	137–138
10	2	H	C20H20O5S	374.1	94	116–117
11	3	H	C21H22O5S	386.1	94	110–111
12	4	H	C22H24O5S	400.1	95	liquid
13	1	Cl	C19H17ClO5S	392.1	96	119–120
14	1	t-Bu	C23H26O5S	414.2	97	85–86
15	1	CF3	C20H17F3O5S	426.1	93	116–117
16	1	OCH3	C20H20O6S	388.1	95	106–107

Scheme 1. Synthesis of (E)-3,4-diacetoxystyryl sulfone and sulfoxide derivatives.

Figure 2. The structure of (E)-3,4-diacetoxystyryl sulfone and sulfoxide derivatives.

Figure 3. Protective effect of compound 7 on 6-OHDA-induced toxicity. PC12 cells in 6-well plates were pretreated by the tested compound for 3 h. Then cells were treated with 500 μM 6-OHDA for 12 h. Compare untreated control cultures (a) with those treated with 6-OHDA (b) and 6-OHDA plus compound 7 (10 μM; (c)) and (40 μM; (d)). Compound 7 significantly attenuated 6-OHDA-induced toxicity as revealed by the cell states.

Table 2. Protective effect of 1–16 on 6-OHDA-induced toxicity of PC12 at 40 μM.

Compound	Cell viability (%)^a	Compound	Cell viability (%)^a
Control	100	6-OHDA	60.0
1 + 6-OHDA	83.6	9 + 6-OHDA	89.2
2 + 6-OHDA	99.7	10 + 6-OHDA	96.0
3 + 6-OHDA	94.6	11 + 6-OHDA	89.1
4 + 6-OHDA	92.6	12 + 6-OHDA	76.9
5 + 6-OHDA	96.6	13 + 6-OHDA	96.4
6 + 6-OHDA	69.8	14 + 6-OHDA	72.2
7 + 6-OHDA	99.8	15 + 6-OHDA	99.5
8 + 6-OHDA	86.4	16 + 6-OHDA	92.4

^aPC12 cells in 96-well plates were pretreated by the tested compound for 3 h. Then, cells were treated with 400 μM 6-OHDA for 48 h. Cell viability was determined by the MTT assay. The viability of untreated cells as control is defined as 100%.

Figure 4. Compound 3 at 2, 4 and 8 μM inhibit H₂O₂-induced cell injury. PC12 cells in 96-well plates were pretreated by the tested compound for 3 h. Then the cells were treated with 500 μM H₂O₂ for 5 h. Cell viability was determined by the MTT assay. The viability of untreated cells as control is defined as 100%.

Table 3. Inhibition effects of H₂O₂-induced cell injury of 1–16 in PC12 cells at 5 μM.

Compound	Cell viability (%)^a	Compound	Cell viability (%)^a
Control	100	H2O2	23.8
1 + H2O2	54.0	9 + H2O2	45.5
2 + H2O2	74.1	10 + H2O2	54.7
3 + H2O2	81.2	11 + H2O2	80.9
4 + H2O2	67.1	12 + H2O2	70.0
5 + H2O2	77.0	13 + H2O2	74.1
6 + H2O2	80.1	14 + H2O2	68.6
7 + H2O2	69.1	15 + H2O2	78.6
8 + H2O2	51.7	16 + H2O2	33.1

^aPC12 cells in 96-well plates were pretreated by the tested compound for 3 h. Then, the cells were treated with 500 μM H₂O₂ for 5 h. Cell viability was determined by the MTT assay. The viability of untreated cells as control is defined as 100%.

Table 4. Suppression effects of LPS induced NO production of 1–16 in BV2 microglial cells.

Compound	IC50 (µM)^a	Compound	IC50 (µM)^a
1	11.5 ± 0.8	9	30.3 ± 1.7
2	34.9 ± 1.5	10	46.6 ± 3.3
3	14.0 ± 0.7	11	10.2 ± 0.2
4	15.9 ± 0.3	12	41.7 ± 2.0
5	8.9 ± 0.5	13	9.4 ± 0.8
6	6.3 ± 0.2	14	8.0 ± 0.2
7	7.9 ± 0.5	15	9.1 ± 0.6
8	9.9 ± 0.8	16	19.0 ± 1.8

^aData are expressed as the mean ± SD, n = 3.