Stability, cytotoxicity, and saturation effect of the free radical-scavenging cinnamic acid-dopamine hybrid antioxidants

doi:10.5246/jcps.2015.03.018

Abstract

Abstract:

Hybrid antioxidants cinnamoyldopamine (2a), p-coumaroyldopamine (2b), caffeoyldopamine (2c), feruloyldopamine (2d) and sinapoyldopamine (2e) were synthesized by conjugation of dopamine (DA) and hydroxycinnamic acids (HCAs). The stabilities were studied in buffers at pH 1.3, pH 5.0, and pH 7.4 including the human plasma. All the compounds were found highly stable at acidic pH, but underwent hydrolysis at neutral pH. Furthermore, the hydrolysis proceeded much faster in plasma in the following order as indicated by half-life values (t_1/2), 2c (1.21 h)<2e (1.52 h)<2d (1.85 h)<2b (3.38 h)<2a (3.88 h), correlating with the number of electron-donating groups. It has been proven by UV spectrum that 2c, 2d, and 2e displayed red shift of more than 50 nm as compared to 2a and 2b, because of the presence of OH and OCH₃groups. In addition, the compounds (2b–e) showed no cytotoxicity on normal HUVEC cells as DA, although 2a displayed a 16% inhibition of proliferation at 40 μM following 48 h incubation. Their free radical-scavenging activities were evaluated using ABTS^•+and superoxide anion assays and the mechanisms were proposed. It was found that they all exhibited higher activities than trolox, a recognized antioxidant. Amazingly, in the case of the hybrids (2a–e), their activity was higher than that of HCAs while lower or comparable to that of DA, suggesting that there may be a “saturation effect” with the hybrid molecules in the antioxidant activities.

Key words: Dopamine, Hydroxycinnamic acid, Free radical-scavenging activity, Cytotoxicity, Stability

CLC Number:

R916.2

Supporting:

Fenfen Yin, Zhengrong Wu, Lifang Zheng, Hongyu Li, Beining Chen. Stability, cytotoxicity, and saturation effect of the free radical-scavenging cinnamic acid-dopamine hybrid antioxidants[J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(3): 148-155.

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