含氨基酸片段的膦酸酯衍生物合成与抗肿瘤作用

Synthesis and antitumor activity of phosphonate derivatives containing amino acid

摘要: 采用基于片段的药物发现方法，对前期研究的膦酸酯化合物进行优化，寻找抗肿瘤先导化合物。设计合成了15个含氨基酸片段的膦酸酯衍生物，经IR、¹H NMR、¹³C NMR及元素分析确认结构。采用溴化噻唑蓝四氮唑（MTT）法进行了初步体外抗肿瘤细胞增殖活性研究。结果表明：目标化合物呈现不同的抗肿瘤活性，其中化合物4e、4n对A-549有明显增殖抑制作用，IC₅₀分别为8.7±0.8、8.2±1.0 μmol·L^-1；化合物4c对SGC-7901的IC₅₀为9.8±0.9 μmol·L^-1；化合物4l、4n对肿瘤细胞EC-109的增长具有显著抑制作用，IC₅₀分别为9.5±0.6、9.4±0.5 μmol·L^-1。

Abstract: In search of effective anticancer agents, fifteen new phosphonate derivatives were designed and synthesized. Their structures were clearly established by elemental analysis, IR, ¹H NMR and ¹³C NMR, and their antitumor activities were evaluated by MTT assay. Preliminary results in bioactivity tests indicated that some title compounds exhibited better activity. Among the active compounds, compounds 4e, 4n had better inhibition effect on A-549 cells growth with IC₅₀ values of 8.7±0.8, 8.2±1.0 μmol·L^-1, the IC₅₀ values of compound 4c was 9.8±0.9 μmol·L^-1 against SGC-7901 cells and compounds 4l, 4n exhibited more potent activities against EC-109 with IC₅₀ values of 9.5±0.6, 9.4±0.5 μmol·L^-1.