Dagmar Ísleifsdóttir and Elvar Örn Viktorsson
Introduction:
Antimicrobial resistance is a major threat to global health and the emergence of drug-resistant pathogens is rising faster than the development of new and effective antimicrobial treatments. Resistant fungi are becoming a serious problem world-wide. Phenazines are a group of heterocyclic compounds reported to possess diverse biological activities, including antibiotic, antifungal, and antitumor properties. Among them, myxin and iodinin – two phenazine 5,10-dioxide natural products, have demonstrated potent antimicrobial activities in vitro, indicating their potential for the development of new antimicrobial agents.
Methodology:
1-hydroxyphenazine and its corresponding dioxide, 1-hydroxyphenazine 5,10-dioxide were synthesized. The starting compounds were then further subjected to O-alkylations and/or chlorinations to synthesize a set of analogs with close structural similarities. The antifungal activity of the synthesized compounds, myxin and iodinin were evaluated by a disk diffusion assay against C. albicans, C. glabrata and C. krusei.
Results:
N-oxides were confirmed to play an important role in the potent antifungal activity of the compounds, and similar or increased antifungal activity was observed in O-alkylated 1-hydroxyphenazine 5,10-dioxide analogs when compared to myxin.
Conclusions:
The potent antifungal activity of several phenazine 5,10-dioxide analogs synthesized during this research highlights their potential as lead structures for the development of novel and effective antimicrobial agents and warrants further investigation into their structure-activity relationships and lead optimization.
