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近年研究表明,炎症和癌症都与花生四烯酸的代谢产物环氧酶和5-脂氧酶密切相关。据此选择对环氧酶或5-脂氧酶具有抑制作用的苯丙烯酸类化合物作为抗炎、抗癌先导化合物,并对其酯类衍生物及其苯乙烯酮类类似物进行初步探讨。本文作者设计并合成上述类型化合物共十九个,其中十五个为未见文献报道的新化合物,并经红外光谱、~1H-核磁共振光谱及元素分析等证实其化学结构。对所合成的化合物进行了抗炎及抗癌药理活性初步筛选。体内抗炎实验表明,所合成的苯丙烯酸类化合物Ⅰ_A,Ⅰ_B,Ⅰ_C人及其酯类衍生物Ⅱ_(2A),Ⅱ_(2C),Ⅱ_(5C)和苯乙烯酮类似物Ⅲ_C对巴豆油诱发的小鼠耳廓肿胀均有不同程度和抑制作用。体外抗癌作用初步筛选结果表明,化合物Ⅰ_B,Ⅱ_(5A),Ⅱ_(5C),及Ⅲ_D对HL-60人癌细胞均有较好的抑制作用。值得注意的是,化合物Ⅰ_B和Ⅱ_(5C)不仅对体外HL-60人癌细胞具有明显的抑制作用,而且对巴豆油所致小鼠炎症亦有较强的活性。深入的药理实验还在进行中。
Recent studies show that both inflammation and cancer are closely related to cyclooxygenase and 5-lipoxygenase, the metabolites of arachidonic acid. Based on this, phenyl acrylates, which have the inhibitory effect on cyclooxygenase or 5-lipoxygenase, were selected as the anti-inflammatory and anticancer lead compounds. Their ester derivatives and their derivatives of styrylketones were also discussed. The authors design and synthesize a total of 19 compounds of the above types, of which 15 are novel compounds that have not been reported in the literature. Their chemical structures were confirmed by IR, ~ 1H-NMR and elemental analysis. The synthesized compounds were initially screened for anti-inflammatory and anti-cancer pharmacological activity. In vivo anti-inflammatory experiments showed that the synthesized acrolein Ⅰ_A, Ⅰ_B, Ⅰ_C and its ester derivatives Ⅱ 2A, Ⅱ 2C, Ⅱ_ (5C) and Styryl ketone analog III_C induced by croton oil Mouse ear swelling have different degrees and inhibition. The results of preliminary screening in vitro showed that compounds Ⅰ_B, Ⅱ_ (5A), Ⅱ_ (5C) and Ⅲ_D inhibited HL-60 human cancer cells effectively. It is worth noting that compounds Ⅰ_B and Ⅱ_ (5C) not only have obvious inhibitory effect on HL-60 human cancer cells in vitro, but also have strong activity on the inflammation induced by croton oil in mice. In-depth pharmacological experiments are still underway.