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

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2020 Nov 2

PMID 33134730

Citations 8

Authors

Haruki Kohatsu

Shogo Kamo

Masateru Furuta

Shusuke Tomoshige

Kouji Kuramochi

Affiliations

Soon will be listed here.

Abstract

In this study, the synthesis of -alkyl-2-halophenazin-1-ones has been established. Six -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 -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 -alkyl-2-chlorophenazin-1-ones. The traditional chlorination of -alkyl-phenazin-1-ones with -chlorosuccinimide selectively occurs at the 4-position to afford the undesired -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 -alkyl-2-halophenazin-1-ones and three -alkylphenazin-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.

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