苯丙烯酸类衍生物和类似物的合成及其抗炎和抗癌活性研究(英文)

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。

SYNTHESIS,ANTIINFLAMMATORY AND ANTICANCER ACTIVITY OF CINNAMIC ACIDS,THEIR DERIVATIVES AND ANALOGUES

Cinnamic acids were selected as lead compounds of antiinflammatory and anticancer agents through the investigation of their biological properties. Their esters and related styryl ketones were also studied. A total of nineteen compounds, fifteen of them not reported previously, were synthesized and found to be of considerable pharmacological interest. In preliminary biological tests, compounds IA, IB, IC, II2C and II5C showed significant inhibiting effect on croton oil induced mouse ear edema, IB, II5A, II5C and IIID exhibited good activity on HL-60 human cancer cells in vitro. It is well worth noticing that compounds IB and II5C exhibited excellent antiinflammatory action as well as anticancer activity.