68-81-5Relevant articles and documents
Dual phenazine gene clusters enable diversification during biosynthesis
Shi, Yi-Ming,Brachmann, Alexander O.,Westphalen, Margaretha A.,Neubacher, Nick,Tobias, Nicholas J.,Bode, Helge B.
, p. 331 - 339 (2019/04/17)
Biosynthetic gene clusters (BGCs) bridging genotype and phenotype continuously evolve through gene mutations and recombinations to generate chemical diversity. Phenazine BGCs are widespread in bacteria, and the biosynthetic mechanisms of the formation of the phenazine structural core have been illuminated in the last decade. However, little is known about the complex phenazine core-modification machinery. Here, we report the diversity-oriented modifications of the phenazine core through two distinct BGCs in the entomopathogenic bacterium Xenorhabdus szentirmaii, which lives in symbiosis with nematodes. A previously unidentified aldehyde intermediate, which can be modified by multiple enzymatic and non-enzymatic reactions, is a common intermediate bridging the pathways encoded by these BGCs. Evaluation of the antibiotic activity of the resulting phenazine derivatives suggests a highly effective strategy to convert Gram-positive specific phenazines into broad-spectrum antibiotics, which might help the bacteria–nematode complex to maintain its special environmental niche.
Total synthesis and antileukemic evaluations of the phenazine 5,10-dioxide natural products iodinin, myxin and their derivatives
Viktorsson, Elvar ?rn,Melling Gr?the, Bendik,Aesoy, Reidun,Sabir, Misbah,Snellingen, Simen,Prandina, Anthony,H?gmoen ?strand, Ove Alexander,Bonge-Hansen, Tore,D?skeland, Stein Ove,Herfindal, Lars,Rongved, P?l
supporting information, p. 2285 - 2293 (2017/03/24)
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.
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Page/Page column 22; 23, (2015/05/19)
The invention provides novel phenazine derivatives, methods for their preparation and their medical use, in particular as anti-neoplastic agents and anti- infective agents. The invention further relates to novel methods for the preparation of iodinin and
