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

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.

• Authors: 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
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 25 Issue 7 Pg. 2285-2293 (04 01 2017) ISSN: 1464-3391 [Electronic] England
• PMID: 28284865 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Biological Products
• Phenazines
• myxin
• iodinin

Topics

• Biological Products (chemical synthesis, pharmacology)
• Cell Line, Tumor
• Humans
• Phenazines (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship