Synthesis and in vitro antitumor activity of isoazamitosene and isoiminoazamitosene derivatives

Chan Mug Ahn, Soo Kie Kim

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Seven isoazamitosene derivatives, mitomycin analogues, were synthesized and tested for cytotoxicities against leukemia and gastric cancer cell lines. Preparation of a pyrrolo[1,2-a]benzimidazole (3) (azamitosene ring system) was completed by utilizing the Lewis acid-catalized cyclization, with o-chloronitrotoluene as the starting material. Nitration of 3 produced a mixture of two isomers (5-nitro isomer (4) and 7-nitro isomer (5)) in product ratio of 36 : 52. 4 was directly converted into quinone (7) by reduction and Fremy oxidaton. Finally, quinone derivatives (8, 9, 10, and 11) were synthesized by 1,4-addition of 7 with cyclic secondary amines. From above-mentioned 5, 8-nitro compound (15) was prepared in 4 steps. At pH 3, Fremy oxidation of 15 produced quinone (16), whereas iminoquinone derivatives (17a and 17b) at pH 7. Isoazamitosene derivatives (8, 9, 10, and 11), containing cyclic amino groups at the 7-position, showed potent cytotoxicity on P388, SNU-1, and KHH tumor cell lines. Among them, 8 had stronger cytotoxicity against SNU-1 cell line than mitomycin and adriamycin. Considering these results, isoazamitosene derivatives may had unique cytotoxicity profiles. However, isoiminoazamitosene derivatives (17a and 17b) revealed very weak cytotoxicity.

Original languageEnglish
Pages (from-to)535-542
Number of pages8
JournalArchives of pharmacal research
Volume19
Issue number6
DOIs
Publication statusPublished - 1996 Dec

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry

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