Antioxidant and neuroprotective effects of synthesized sintenin derivatives

Figures & data

Figure 1.  The structures of sintenin and three series of synthetic sintenin derivatives.

Scheme 1 Synthesis of compound 5. Reagents and conditions: (i) CDI, THF, reflux, 0.5 h; DBU, THF, reflux, 12 h.

Scheme 2 Synthesis of compounds 6–8. Reagents and conditions: (i) DCC, CH₂Cl₂, rt, 5 min; DMAP, rt, 12 h (ii) 10% HCl, CH₃OH, reflux.

Table I.  DPPH radicals scavenging activity by the test compounds.

Compounds	DPPH inhibition (50 μg/mL)
1	11.20%
2	18.60%
3	16.80%
4	35.8 ± 5.4^a
5	13.40%
6	3.10%
7	14.20%
8	–^b
9	14.00%
10	–^b
11	0.70%
12	1.10%
13	20.0 ± 4.0^a
14	–^b
Quercetin	11.9 ± 0.43^a

^a IC₅₀ ± SD (μM): IC₅₀ values were further generated for those inhibitions greater than 50% at the concentration of 50 μg/mL. Data are expressed means ± SD, n = 3

^b No detectable activity.

Figure 2.  The inhibitory effects of compounds 4, 13, curcumin, and quercetin on iron-induced lipid peroxidation in rat brain homogenates.

Table II.  Ferrous ion chelating ability by the test compound.

Compounds	Ferrous ions chelation (110 μg/mL)
1	10.0%
2	2.4%
3	21.2%
4	75.1 ± 4.9%^a
5	6.4%
6	10.4%
7	7.2%
8	4.8%
9	12.4%
10	11.2%
11	10.4%
12	14.4%
13	40.4%
14	14.8%
Quercetin	46.8%

^a Data are shown as means ± SD, n = 3.

Figure 3.  Effects of compounds 4, 13 and positive control on PC 12 cell injury induced by H₂O₂. (A) PC 12 control cells. (B) PC 12 cells exposed to 600 μM of H₂O₂ for 3 h. Most of the cells become round shapes. The membrane lesion of cells was also observed. (C, D and E) PC 12 cells were pre-incubated with 20 μg/mL of compounds 4, 13 and quercetin, respectively before exposed to 600 μM H₂O₂ for 3 h.

Figure 4.  Protective effects of compounds 4, 13, and quercetin against H₂

induced insult in PC 12 cells. The experiments were repeated three times. *p < .01, compared with the negative control.

Figure 5.  The results of removing test compounds from the pre-incubated medium of PC 12 cells prior to the injury initiated by H₂O₂. (A) PC 12 control cells. (B) PC 12 cells exposed to 600 μM H₂O₂ for 3 h. Most of the cells become round shapes. The membrane lesion of cells was also observed. (C, D and E) PC 12 cells were pre-incubated with 20 μg/mL of compounds 4, 13 and quercetin, respectively, and then the compounds were removed from the medium and the cells were exposed to 600 μM H₂O₂ for 3 h. The cells cultured with compounds 4 and 13 were remarkably improved in cell viabilities and integralities.