N-乙酰基-S-烯丙基-L-半胱氨酸的合成及其抗辐射活性

以L-半胱氨酸为原料,经取代和酰化两步反应合成目标产物N-乙酰基-S-烯丙基-L-半胱氨酸(N-acetyl-S-allyl-L-cysteine,NAc-SAC)。以~(137)Csγ射线照射至不同剂量的ICR小鼠作为研究对象,通过30 d存活率实验、血相和免疫系统实验、各项脏器指数以及外周血淋巴细胞彗星实验,研究目标化合物分别在200、400、600 mg/kg给药剂量下的抗辐射活性。ICR小鼠经伽马射线照射至致死剂量7.5 Gy后,其存活率由单纯照射对照组的41.6%,分别提高到NAc-SAC给药组的58.3%、50.0%和66.7%,平均存活天数明显延长。~(137)Csγ射线照射至亚致死剂量6.0 Gy后,NAc-SAC在不同程度上增加了受照小鼠的脾指数、脾结节数(CFU-S)、骨髓DNA含量和白细胞数。彗星实验中7.0 Gy伽马射线照射联合NAc-SAC给药组小鼠外周血淋巴细胞的尾长、尾矩、Olive尾矩和尾部DNA百分含量明显低于7.0 Gy伽马射线单纯照射组(p0.01),提示NAc-SAC可明显降低辐射导致的DNA损伤。本研究表明,目标化合物NAc-SAC具有一定的抗辐射损伤作用。

Synthesis and anti-irradiation activities of N-acetyl-S-allyl-L-cysteine

The N-acetyl-S-allyl-L-cysteine (NAc-SAC) was synthesized by substitution and acylation reactions with L-cysteine as raw materials. Experiments on blood and immune-organs indexes, and survival rates of ICR mice within 30 d after137Cs γ-rays irradiation at different doses, as well as the comet assay were carried out to investigate the anti-irradiation effects of NAc-SAC. The survival rates of mice irradiated at 7.5 Gy with the dose of NAc-SAC at 200 mg/kg, 400 mg/kg, and 600 mg/kg increased to 58.3%, 50.0% and 66.7%, respectively, and the average survival time was significantly prolonged compared with that in the control group. The spleen indexes, colony forming cell-spleen (CFU-S), percentages of DNA, number of white blood cells of mice irradiated at 6.0 Gy increased under the action of NAc-SAC. The tail length, tail moment, olive tail moment, and tail DNA percentage of peripheral blood lymphocytes of mice irradiated at 7.0 Gy combined with NAc-SAC were higher than those for the control group (p<0.05). To conclude, NAc-SAC has a protective effect against damage induced by irradiation.