1-单取代萘醌及蒽醌并咪唑衍生物的设计合成和抗肿瘤活性研究（英文）

Design, Synthesis and Antitumor Activity of 1-Monosubstituted 1H-Naphtho[2,3-d]imidazole-4,9-diones and 1H-Anthra[2,3-d]imidazole-4,11-diones

为了进一步拓展醌并咪唑类化合物的分子多样性以获得更高的抗肿瘤活性和选择性,设计合成了一系列1-单取代的萘醌及蒽醌并咪唑衍生物.经细胞毒性实验发现,其中具有大共轭体系和小位阻取代基的1-甲基蒽醌并咪唑显示出优于此前报道的1,2-二取代萘醌并咪唑衍生物的抗肿瘤活性和选择性.其对乳腺癌细胞和非小细胞肺癌细胞具有很好的抗恶性增殖活性(IC_(50)=7.4和1.6μmol·L^(-1)),而对正常细胞L929则几乎不显示毒性(IC_(50)=150μmol·L^(-1)).

In order to further expand the molecular diversity of quinone-fused imidazoles as anticancer agents, a number of1-monosubstituted 1H-naphtho[2,3-d]imidazole-4,9-diones and 1H-anthra[2,3-d]imidazole-4,11-diones were designed, synthesized and biologically evaluated. The structure-activity relationships were studied in vitro against three human cancer cell lines(human breast carcinoma cell line MCF-7, human cervical carcinoma cell line Hela and human lung carcinoma cell line A549)and one normal cell line(mouse fibroblast cell line L929). Among them, 1-methyl-1H-anthra[2,3-d]imidazole-4,11-dione, which bears a large π-system and a small N-substituent in the imidazole segment, showed good antiproliferative activity against MCF-7 and A549(IC50 values are 7.4 and 1.6 μmol·L^-1, respectively) and almost no cytotoxicity to L929(IC50 is 150 μmol·L^-1).