|
KMID : 0043319980210050599
|
|
Archives of Pharmacal Research
1998 Volume.21 No. 5 p.599 ~ p.609
|
|
|
Synthesis of 6-Aziridinylbenzimidazole Derivatives and Their In Vitro Antitumor Activities
|
|
Ahn Chan-Mug
Kim Soo-Kie
Han Jeong-Lim
|
|
|
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.
|
|
|
KEYWORD
|
|
|
Benzimidazole, Cytotoxicity, Azamitosene
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|