【摘要】 基于酶与底物的相互作用原理,将安曲霉素核心骨架吡咯骈苯并二氮杂卓中关键的不对称碳原子替换为氮原子,利用三取代氮易于在R和S构型间相互转化的特性,以及DNA小沟区手性环境对配体的诱导契合作用,设计并合成了11个新型的N-杂安曲霉素衍生物（8a⁸g,9a⁹d）。以邻氨基苯甲酸衍生物为原料,先与三聚光气反应制得靛红酸酐衍生物,再与六氢哒嗪发生开环反应,最后与三聚光气发生环化反应合成目标产物,其结构经¹H NMR,¹³C NMR,IR和HR-MS（ESI）表征。并研究了化合物对肿瘤细胞的体外生长抑制活性及与DNA的相互作用。结果表明:8a⁸e对人肺癌细胞（NCI-H460）,人宫颈癌细胞（Hela）和人胃癌细胞（MGC-803）有一定的抑制活性,IC₅₀为19⁴7μmol·L^-1。8d与超螺旋DNA有弱相互作用。更多还原

【Abstract】 Based on the interaction principle of the substrates and enzyme,the R/S configuration interconversion property of trisubstitution nitrogen and the induce-fit effect of DNA chiral environment,eleven novel aza-anthramycin derivatives（8a⁸g,9a⁹d）in which the key chiral carbon atom of the anthramycin’s pyrrolo-benzodiazepines nucleus was replaced by an nitrogen atom were designed and synthesized via a three-step reaction,including the reaction of anthranilic acid derivatives with triphosgene to give the isatoic anhydrides,followed by ring-opened reaction with hexahydropyridazine and a ring-closed reaction with triphosgene.The structures were characterized by¹H NMR,¹³C NMR,IR and HR-MS（ESI）.The in vitro inhibition activities of target compounds against tumor cell lines（NCI-H460,Hela and MGC-803）and the interaction with DNA were evaluated.The results revealed that,to some extent,8a,8b,8c and 8e exhibited cytotoxicity against the tested cell lines,with IC₅₀of 19⁴7μmol·L^-1.In addition,8d display weak capability to interact with supercoiled DNA.更多还原