Synthesis and Cytotoxic Evaluation of N-Alkyl-2-halophenazin-1-ones

Haruki Kohatsu, Shogo Kamo, Masateru Furuta, Shusuke Tomoshige, Kouji Kuramochi

Research output: Contribution to journalArticlepeer-review

Abstract

In this study, the synthesis of N-alkyl-2-halophenazin-1-ones has been established. Six N-alkyl-2-halophenazin-1-ones, including WS-9659 B and marinocyanins A and B, were synthesized by the direct oxidative condensation of 4-halo-1,2,3-benzenetriol with the corresponding N-alkylbenzene-1,2-diamines. One of the most significant features of the present method is that it can be successfully applied to the synthesis of N-alkyl-2chlorophenazin-1-ones. The traditional chlorination of N-alkylphenazin-1-ones with N-chlorosuccinimide selectively occurs at the 4-position to afford the undesired N-alkyl-4-chlorophenazin-1-ones. Our synthetic route successfully circumvents this problem, culminating in the first chemical synthesis of WS-9659 B. The cytotoxicity of six N-alkyl-2-halophenazin-1-ones and three Nalkylphenazin-1-ones against human promyelocytic leukemia HL-60, human lung cancer A549, and normal MRC-5 cells was evaluated. Among the compounds tested in this study, 2-chloropyocyanin possesses significant selectivity toward A549 cells. The cytotoxic evaluation provides structural insights into the potency and selectivity of these compounds for cancer cells.

Original languageEnglish
Pages (from-to)27667-27674
Number of pages8
JournalACS Omega
Volume5
Issue number42
DOIs
Publication statusPublished - 2020 Oct 27
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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