title: Synthesis of 6-aziridinylbenzimidazole derivatives and their in vitro antitumor activities.
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 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.
authors.affiliation: Department of Basic Sciences, Wonju College of Medicine, Yonsei University, Korea.
authors.forename: C M
authors.initials: CM
authors.lastname: Ahn
authors.forename: S K
authors.initials: SK
authors.lastname: Kim
authors.forename: J L
authors.initials: JL
authors.lastname: Han
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001388:Aziridines / Q000138:chemical synthesis* / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007202:Indicators and Reagents; D051379:Mice; D009580:Nitroblue Tetrazolium; D010084:Oxidation-Reduction; D011809:Quinones / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001388:Aziridines; D001562:Benzimidazoles; D007202:Indicators and Reagents; D011809:Quinones; D009580:Nitroblue Tetrazolium