N9位芳基取代嘌呤-8-酮类衍生物的合成及抗肿瘤活性

合成了一系列N9位芳基取代嘌呤-8-酮类衍生物, 利用核磁共振氢谱(¹H NMR)、 核磁共振碳谱(¹³C NMR)和高分辨质谱(HRMS)进行了结构确证. 采用四甲基偶氮唑盐(MTT)法测定了目标化合物的体外抗肿瘤细胞增殖活性. 结果表明, 嘌呤酮环的C2位及N9位的取代对活性有较大影响, C2位引入对位由含氮六元环取代的苯胺, N9位引入对三氟甲基苯均有利于提高抗肿瘤活性. 化合物12c对人白血病细胞(K562)、 人前列腺癌细胞(PC-3)、 人乳腺癌细胞(MDA-MB-231)及人结肠癌细胞(HCT116)的抑制效果明显优于阳性对照药R-Roscovitine.

Synthesis and Antitumor Activity of N9 Position Aromatic Substituted Purine-8-one Derivatives†

A series of novel N9 position aromatic substituted purine-8-one derivatives was synthesized and the antitumor activities were evaluated in vitro. Chemical structures of target compounds were confirmed by means of nuclear magnetic resonance(NMR) and high resolution mass spectroscopy(HRMS). The antiproliferative acti-vities of target compounds were tested on a panel of tumor cell lines using thiazolyl blue tetrazolium bromide(MTT) assay. The results revealed that the substitutions on C2 and N9 position had great impacts on antitumor activities. Moreover, introducing aniline attached six-member ring on C2 position or p-CF₃ on N9 position could improve the antitumor activities. Importantly, the most potent compound 12c exhibited better inhibitory activities than R-Roscovitine against four tumor cell lines, including human leukemia cell lines(K562), human prostatic carcinoma cell lines(PC-3), human breast cancer cell lines(MDA-MB-231) and human colon cancer cell lines(HCT116).