Synthesis, Crystal Structure and Bioactivity of Phenazine-1-carboxylic Acylhydrazone Derivatives

Abstract

A phenazine-1-carboxylic acid intermediate was synthesized from the reaction of aniline and 2-bromo-3-nitro-benzoic acid. It was then esterified and reacted with hydrazine hydrate to afford phenazine-1-carboxylic hydrazine. Finally, 10 new hydrazone compounds 3a–3j were obtained by the condensation reaction of phenazine-1-carboxylic acid hydrazide and the respective aldehyde-containing compound. The structures were characterized by 1H and 13C NMR spectroscopy, MS and single crystal X-ray diffraction. The antitumor activity of the target compounds in vitro (HeLa and A549) was determined by thiazolyl blue tetrazolium bromide. The results showed that compound (E)-N′-(2-hydroxy-4-(2-(piperidine-1-yl) ethoxy) benzyl) phenazine-1-carbonyl hydrazide 3d exhibited good cytotoxic activity.

Economical Production of Phenazine-1-carboxylic Acid from Glycerol by Pseudomonas chlororaphis Using Cost-Effective Minimal Medium

“…However, some industries still rely on chemical synthesis for manufacturing the required products, which should be reformed in order to achieve better sustainability. The chemical synthesis of phenazine compounds, which exhibit high inhibitory activity against pathogens and antitumor activity, is a typical case, requiring strict reaction conditions (e.g., aqueous alkali, high temperature) and possibly producing some toxic by-products [4,5]. The microbial synthesis of phenazine compounds (e.g., phenazine-1-carboxylic acid, PCA; phenazine-1-carboxamide, PCN; and 2-hydroxyphenazine, 2-OH-PHZ) is an alternative to chemical synthesis, attracting more and more attention due to its mild reaction conditions and green and sustainable process.…”