β-内酰胺类螺环化合物的设计、合成及细胞毒活性研究

Design,synthesis and cytotoxic activity of β-keto-lactams compounds

从脂肪族和芳香族的伯胺出发,利用催化量的铜盐灵活高效催化合成一系列结构新颖的内酰胺类螺环化合物.经~1H NMR,^(13)C NMR,X单晶衍射确定其结构,并对新合成的化合物进行了体外抗肿瘤细胞毒活性筛选.结果表明,其中化合物7a-13和7a-15具有较好的体外肿瘤生成抑制活性,对SW-480肿瘤细胞株的活性均优于顺铂,化合物7a-16对MCF-7和SW-480这2种肿瘤细胞株表现出较好的选择性细胞毒活性,其IC_(50)值约为顺铂的2.0倍.

In the presence of catalytic amount of copper salt, an efficient and flexible synthetic method towards the synthesis of a structurally new type of spirocyclic lactams was developed. Their structures were confirmed by ^1H NMR, ^13C NMR,HR-MS and X-ray crystallographic analysis.These compounds were evaluated in vitro against a panel of human tumor cell lines.The results showed that compounds 7a-12 and 7a-13 exhibited higher inhibitory activity selectively against MCF-7 and SW480 cell lines compared with DDP.ln particular, compound 7a-16 was more selective to SW-480 cell lines with IC50 values 2.0-fold lower than DDP.