Synthesis and biological evaluations of new O-acylated phenazine 5,10-dioxides

Abstract

Synthesizing and modifying naturally occurring compounds has played a major role in the war against the ever-evolving bacteria. Phenazines are one such natural class of compounds, originally found in P. aeruginosa. Some of the compounds found in this class have shown potential for their antibiotic or antineoplastic effects, such as iodinin and myxin.The aim of this study was to synthesize and characterize ester analogs of 1,3-dihydroxyphenazine 5,10-dioxide (1). This was done by synthesizing two phenazine scaffolds. 1,3-Dihydroxyphenazine 5,10-dioxide (1), a regioisomer of iodinin and 2-hydroxyphenazine 5,10-dioxide (2). Compound 2 was meant to serve as a convenient phenazine scaffold for method development of O-acylation reactions. The ester analogs were synthesized by exposing 1 or 2 to acetyl chloride, thereby O-acylating the phenol oxygen atoms resulting in formation of ester analogs. This synthesis afforded a total of 4 new analogs of both 1 and 2. The purity, chemical structure and mass of each successfully synthesized compound was confirmed with the use of HPLC, 1H-NMR, 13C-NMR and HRMS.Then after successful characterization of all the compounds their antimicrobial effects were explored in vitro with a Disk Diffusion assay. They were tested against S. aureus and P. aeruginosa. Four out of the seven synthesized analogs and myxin presented activity against S. aureus and only myxin had an effect against P. aeruginosa. None of them produced as large or larger inhibition zones as myxin.