新型E-2,3-二芳基丙烯酰氧基膦酸酯衍生物的设计、合成与抗肿瘤活性

Design, synthesis and antitumor activities of novel E-substituted 2, 3-diaryl propenoic acyloxy phosphonate derivatives

根据活性片段组合原理,设计、合成了一系列新型E-2,3-二芳基丙烯酰氧基膦酸酯衍生物,结构经IR、1H NMR、13C NMR及元素分析确证。采用MTT法测试目标化合物的抗肿瘤活性。结果表明:部分化合物对于所测试肿瘤细胞有抑制作用,其中化合物3e对A-549的活性[IC50=(12.7±1.9)μmol·L-1]最为突出,与对照药顺铂[IC50=(8.0±1.5)μmol·L-1]较为接近;化合物3g、3k对EC-109的增殖抑制作用最好,IC50分别为(9.5±1.8)μmol·L-1和(11.5±0.9)μmol·L-1;化合物3i、3k对SGC-7901、A-549、EC-109三种肿瘤细胞均有较好抑制作用。该类衍生物值得进一步研究。

According to the super-position principle of the reinforcement of biological activities, a series of novel E-substituted 2, 3-diaryl propenoic acyloxy phosphonate derivatives were designed and synthesized. And the structures of the target compounds were confirmed by IR, 1H NMR, 13 C NMR and elemental analysis. Furthermore, the cytotoxicities of all compounds on A-549, SGC-7901 and EC-109 in vitro were evaluated by MTT assay, and some of them showed good antitumor activity. Among the active compounds, especially, the IC50 value of compound 3e was（12.7 ± 1.9） μmol·L-1 against A-549 cells, similar to cisplatin [IC50 =（8.0 ± 1.5） μmol·L-1], compounds 3g and 3k had better inhibition effect on EC-109 cells growth, with the IC50 values of（9.5 ± 1.8） μmol·L-1 and（11.5 ± 0.9） μmol·L-1 respectively, and compounds 3i and 3k exhibited good cytotoxic property on A-549, SGC-7901 and EC-109, which were worth further investigation.