Synthesis of 6-aziridinylbenzimidazole derivatives and their in vitro antitumor activities

Chan Mug Ahn, Soo-Ki Kim, Jeong Lim Han

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)599-609
Number of pages11
JournalArchives of Pharmacal Research
Volume21
Issue number5
DOIs
Publication statusPublished - 1998 Jan 1

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Cytotoxicity
Benzimidazoles
Cells
Derivatives
Cell Line
Leukemia P388
Lymphoid Leukemia
Quinones
Esterification
Mitomycin
Antineoplastic Agents
Stomach
Esters
Carcinoma
benzimidazole
In Vitro Techniques
Neoplasms

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry

Cite this

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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 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.",
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Synthesis of 6-aziridinylbenzimidazole derivatives and their in vitro antitumor activities. / Ahn, Chan Mug; Kim, Soo-Ki; Han, Jeong Lim.

In: Archives of Pharmacal Research, Vol. 21, No. 5, 01.01.1998, p. 599-609.

Research output: Contribution to journalArticle

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