Comparative study on the antioxidant and anti-Toxoplasma activities of vanillin and its resorcinarene derivative

Abstract

A resorcinarene derivative of vanillin, resvan, was synthesized and characterized by spectroscopic techniques. We measured the cytotoxicity (in vivo and in vitro), antioxidant and anti-Toxoplasma activities of vanillin and the resorcinarene compound. Here we show that vanillin has a dose-dependent behavior with IC50 of 645 µg/mL through an in vitro cytotoxicity assay. However, we could not observe any cytotoxic response at higher concentrations of resvan (IC50 > 2,000 µg/mL). The in vivo acute toxicity assays of vanillin and resvan exhibited a significant safety margin indicated by a lack of systemic and behavioral toxicity up to 300 mg/kg during the first 30 min, 24 h or 14 days after administration. The obtained derivative showed greater antioxidative activity (84.9%) when comparing to vanillin (19.4%) at 1,000 μg/mL. In addition, vanillin presents anti-Toxoplasma activity, while resvan does not show that feature. Our findings suggest that this particular derivative has an efficient antioxidant activity and a negligible cytotoxic effect, making it a potential target for further biological investigations.

Figure 1

Vanillin structure.

Figure 2

Resorcinarene general structure.

Scheme 1

Resvan synthesis scheme.

Figure 3

Electronic spectrum in water of resvan (5.5 × 10⁻⁵ mol L⁻¹) and vanillin (5.8 × 10⁻⁵ mol L⁻¹).

Figure 4

Influence of vanillin and resorcinarene in RAW 264.7 macrophage cell viability after treatment for 24 h. Results are expressed in percentage of control. Three independent experiments are performed in triplicate. (^# p < 0.001 compared to 500, 1,000 and 2,000 µg/mLvanillin treatment).

Figure 5

Antioxidant activity of ascorbic acid, vanillin and resvan assessed by DPPH radical scavenging activities method (^# p < 0.001 compared to 125 µg/mL Ascorbic acid treatment; ° p < 0.01 compared to 500 µg/mL ascorbic acid treatment; * p < 0.05 compared to 1,000 µg/mL ascorbic acid treatment).

Figure 6

Survival curves of Swiss female mice after infection with the ME49 strain of T. gondii and treated with sulfadiazine (200 mg/Kg), resvan (500 mg/Kg) or vanillin (500 mg/Kg).

Figure 7

Change in body weight in Swiss mice infected with 25 cysts of T. gondii ME49 strain and treated with sulfadiazine (200 mg/Kg), resvan (500 mg/Kg) or vanillin (500 mg/Kg).

Figure 8

Number of brain cysts in Swiss mice infected with 25 cysts of T. gondii ME49 strain and treated with sulfadiazine (200 mg/Kg), resvan (500 mg/Kg) or vanillin (500 mg/Kg) (* p < 0.05 compared to sulfadiazine treatment).