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目的本文设计合成了11个2’,4’,6’-三羟基查尔酮衍生物,并对所合成的目标化合物进行抗抑郁活性研究,探讨其可能的作用机制。方法以2’,4’,6’-三羟基苯乙酮为起始原料。经过羟基保护、醇醛缩合、水解三步反应得到目标化合物3a~3k。其结构经IR、1H-NMR和MS等确证。对所合成的目标化合物采用经典抗抑郁模型“小鼠强迫游泳实验”和“小鼠悬尾实验”进行抗抑郁活性研究。采用开放性实验评价化合物3h抗抑郁活性。建立5-羟色氨酸(5-HTP)诱导小鼠甩头和育亨宾小鼠致死增强模型,观察化合物3h对诱导小鼠甩头行为和对小鼠皮下注射(sc)育亨宾致死增强的影响。结果实验结果表明有6个化合物在10 mg/kg剂量下均能明显缩短小鼠强迫游泳不动时间,初步断定其具有抗抑郁活性。其中化合物3h显示最好抗抑郁活性,与氟西汀相似。另外化合物3h在3种不同剂量下(10 mg/kg、20 mg/kg和40 mg/kg)均明显缩短小鼠强迫游泳和小鼠悬尾的不动时间,显示较强的抗抑郁活性,其中在20 mg/kg剂量下显示抗抑郁活性最好。化合物3h也能显著增加5-HTP诱导的小鼠甩头次数,对育亨宾诱导的小鼠致死量没有显著影响。结论 6个查尔酮化合物显示具有明确的抗抑郁作用,其作用机制可能与5-HT系统有关。
OBJECTIVE In this paper, eleven 2 ’, 4’, 6’-trihydroxy chalcone derivatives were designed and synthesized. The antidepressant activity of the target compounds was studied, and its possible mechanism was explored. Methods Starting from 2 ’, 4’, 6’-trihydroxyacetophenone. After the hydroxyl protection, aldol condensation, hydrolysis three steps to give the target compounds 3a ~ 3k. Its structure confirmed by IR, 1H-NMR and MS. The antidepressant activity of the synthesized target compounds was studied by classical antidepressant model “mouse forced swimming test” and “mouse tail suspension test”. Antidepressant activity of compound 3h was evaluated using an open experiment. To establish a lethal model of 5-HTP-induced head-shaved mice and yohimbin-induced death in mice and observe the effect of compound 3h on inducing mouse head-shaving behavior and subcutaneous injection of yohimbine in mice Enhance the impact. Results The experimental results showed that 6 compounds at 10 mg / kg dose could significantly reduce forced swimming time of mice, and initially concluded that they had antidepressant activity. Among them, compound 3h showed the best antidepressant activity, similar to fluoxetine. In addition, compound 3h significantly reduced the forced swimming time and immobility time of mouse tail suspension in 3 different doses (10 mg / kg, 20 mg / kg and 40 mg / kg), showing strong antidepressant activity, Among them, the best antidepressant activity was shown at a dose of 20 mg / kg. Compound 3h also significantly increased 5-HTP-induced shampooing times in mice, yohimbine-induced lethal dose did not have a significant impact. Conclusions Six chalcone compounds show a definite antidepressant effect, which may be related to the 5-HT system.