1种新型喹唑啉类抗癌试剂的合成及其抗癌活性研究

Synthesis of A Novel Quinazoline-Based Anticancer Reagent and Its Anticancer Activity

6-氨基-4-(4-苯氧基苯乙氨基)喹唑啉(QNZ)是一种喹唑啉类NF-κB抑制剂,也是近年来炙手可热的抗癌候选药物之一.抗癌药物阿法替尼有着与QNZ相同的喹唑啉母环结构,并且含有一个Michael受体单元,这种亲电性的药效基团在促氧化抗癌策略中发挥着重要的化学调控作用.基于QNZ与阿法替尼的结构共性,通过分子骨架杂合,设计合成一种新型亲电分子QNZ-Afa.证实了化合物QNZ-Afa在癌细胞中的细胞毒性显著地强于正常细胞,并且以Hela细胞为模型证实了其在癌细胞中的毒性机制:通过促进细胞内活性氧(ROS)的产生从而诱导了细胞凋亡的发生.

6-amino-4-(4-phenoxyphenylethylamino)quinazoline(QNZ),a quinazoline-based inhibitor of NF-κB,has been one of the hot anticancer drug candidates in recent years.There is a same quinazoline-based parent ring as QNZ in the structure of the anticancer drug afatinib,which also contains a Michael acceptor unit.This electrophilic pharmacophore plays an important role in the chemical regulation in pro-oxidation strategies.Based on the structural commonness of QNZ and afatinib,a novel electrophilic molecule QNZ-Afa was designed and synthesized through skeleton hybrid.The cytotoxicity of QNZ-Afa in cancer cells is significantly stronger than that in normal cells.The mechanism of its toxicity in Hela cells was further studied.It is found that QNZ-Afa can promote the intracellular reactive oxygen species(ROS)production to induce the apoptosis in Hela cells.