Ahn C M, Kim S K, Han J L
Department of Basic Sciences, Wonju College of Medicine, Yonsei University, Korea.
Arch Pharm Res. 1998 Oct;21(5):599-609. doi: 10.1007/BF02975382.
In search for new antitumor agents, twelve 6-aziridinylbenzimidazole derivatives were synthesized and their cytotoxicities were tested against three cancer cell lines (mouse lymphocytic leukemia P388 and B16, and human gastric carcinoma SNU-16). From 4-amino-3-nitrotoluene as the starting material, 2-(acetoxymethyl)benzimidazoles (5a-d) were obtained by Phillips reaction. These benzimidazoles were then reacted with Fremy's salt to give a mixture of three 2-(acetoxymethyl) (8a-c) and four 2-(hydroxymethyl)benzimidazole-4,7-diones (9a-d). Addition of these quinones with aziridine afforded 6-aziridinyl-2-(acetoxymethyl) (10a-c) and 6-aziridinyl-2-(hydroxymethyl)benzimidazole-4,7-diones (11a-d). Utilizing 2-(hydroxymethyl)benzimidazole-4,7-diones (9b,d), esters 10d and 13e-h were prepared by the sequential reactions of esterification and addition. The synthesized compounds show potent cytotoxicity against all of three cell lines tested. The cytotoxicities of 10a-d or 11a-d against SNU-16 were superior to those of 13e-h, and were equal to or slightly higher than that of mitomycin C. Compounds 11a-d were slightly more cytotoxic than 10a-d in all cell lines tested.
为了寻找新的抗肿瘤药物，合成了12种6-氮丙啶基苯并咪唑衍生物，并测试了它们对三种癌细胞系（小鼠淋巴细胞白血病P388和B16以及人胃癌SNU-16）的细胞毒性。以4-氨基-3-硝基甲苯为起始原料，通过菲利普斯反应得到2-(乙酰氧基甲基)苯并咪唑(5a-d)。然后这些苯并咪唑与弗勒米盐反应，得到三种2-(乙酰氧基甲基)(8a-c)和四种2-(羟甲基)苯并咪唑-4,7-二酮(9a-d)的混合物。这些醌与氮丙啶加成得到6-氮丙啶基-2-(乙酰氧基甲基)(10a-c)和6-氮丙啶基-2-(羟甲基)苯并咪唑-4,7-二酮(11a-d)。利用2-(羟甲基)苯并咪唑-4,7-二酮(9b,d)，通过酯化和加成的顺序反应制备了酯10d和13e-h。合成的化合物对所有测试的三种细胞系均显示出强效的细胞毒性。10a-d或11a-d对SNU-16的细胞毒性优于13e-h，且与丝裂霉素C相当或略高。在所有测试的细胞系中，化合物11a-d的细胞毒性比10a-d略高。
