一种新型开环烯二炔的设计、合成及细胞毒性研究

Design,Synthesis and Cytotoxicity Study of a Novel Acyclic Enediyne

通过Sonogashira反应合成了一种以马来酰亚胺为主体结构,炔基带有两个对称烷基链的烯二炔化合物。该烯二炔在适度加热的情况下能够发生Bergman环化反应,产生芳基双自由基。通过红外光谱分析确认反应后碳碳叁键信号峰消失;利用自由基捕捉技术获得了单N-叔丁基-α-苯基硝酮(PBN)加成产物和双PBN加成产物,并通过电子顺磁共振波谱检测到了这两种PBN加合物的自由基信号,说明烯二炔发生了Bergman环化反应。MTT法细胞活性实验证实该小分子烯二炔对肿瘤细胞的半抑制浓度在18μmol/L左右,显示出烯二炔对肿瘤细胞具有良好的抗增殖能力。这为以后设计合成高活性的开环型烯二炔抗生素提供了新的思路。

An acyclic enediyne with maleimide as the main structure and two symmetrical alkynyl chains was synthesized through Sonogashira coupling reaction. The enediyne was subjected to thermal Bergman cyclization to yield diradical intermediates. FT-IR results showed the complete conversion of the alkynyl moiety. The diradical intermediates could be further trapped by a spin trap （PBN） to generate mono- and di-PBN adducts corroborating the occurrence of the Bergman cyclization, which was confirmed by EPR analysis. MTT cell activity experiments confirmed that the half inhibitory concentration of this small molecular enediyne on tumor cell was around 18 μmol/L which were stable enough for long-time storage and active enough to suppress the cell multiplication for potential clinical application.