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The Pharmaceutical Society of Korea (대한약학회)
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Synthesis of 6-Aziridinylbenzimidazole Derivatives and Their In Vitro Antitumor Activities

  • Ahn, Chan-Mug (Department of Basic Sciences, Institute of Basic Medical Science, Wonju College of Medicine, Yonsei University) ;
  • Kim, Soo-Kie (Department of Microbiology, Institute of Basic Medical Science, Wonju College of Medicine, Yonsei University) ;
  • Han, Jeong-Lim (Department of Basic Sciences, Institute of Basic Medical Science, Wonju College of Medicine, Yonsei University)
  • Published : 1998.10.01
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Abstract

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 wuperior 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.

Keywords

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