Total synthesis and antileukemic evaluations of the phenazine 5,10-dioxide natural products iodinin, myxin and their derivatives

Elvar Örn Viktorsson, Bendik Melling Grøthe, Reidun Aesoy, Misbah Sabir, Simen Snellingen, Anthony Prandina, Ove Alexander Høgmoen Åstrand, Tore Bonge-Hansen, Stein Ove Døskeland, Lars Herfindal, Pål Rongved*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

A new efficient total synthesis of the phenazine 5,10-dioxide natural products iodinin and myxin and new compounds derived from them was achieved in few steps, a key-step being 1,6-dihydroxyphenazine di-N-oxidation. Analogues prepared from iodinin, including myxin and 2-ethoxy-2-oxoethoxy derivatives, had fully retained cytotoxic effect against human cancer cells (MOLM-13 leukemia) at atmospheric and low oxygen level. Moreover, iodinin was for the first time shown to be hypoxia selective. The structure-activity relationship for leukemia cell death induction revealed that the level of N-oxide functionality was essential for cytotoxicity. It also revealed that only one of the two phenolic functions is required for activity, allowing the other one to be modified without loss of potency.

Original languageEnglish
Pages (from-to)2285-2293
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume25
Issue number7
DOIs
Publication statusPublished - 2017

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Ltd

Other keywords

  • Acute myeloid leukemia
  • Hypoxia selectivity
  • Phenazine 5,10-dioxides
  • Phenazines

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