RESUMO
Starting from the structure of antimycobacterial screening hit OTB-021 which was devoid of activity against ESKAPE pathogens, we designed, synthesized and tested two mutually isomeric series of novel simplified analogs, 2- and 4-(3-nitro-1,2,4-triazol-1-yl)pyrimidines, bearing various amino side chains. These compounds demonstrated a reverse bioactivity profile being inactive against M. tuberculosis while inhibiting the growth of all ESKAPE pathogens (with variable potency patterns) except for Gram-negative P. aeruginosa. Reduction potentials (E1/2, V) measured for selected compounds by cyclic voltammetry were tightly grouped in the -1.3--1.1 V range for a reversible single-electron reduction. No apparent correlation between the E1/2 values and the ESKAPE minimum inhibitory concentrations was established, suggesting possible significance of other factors, besides the compounds' reduction potential, which determine the observed antibacterial activity. Generally, more negative E1/2 values were displayed by 2-(3-nitro-1,2,4-triazol-1-yl)pyrimidines, which is in line with the frequently observed activity loss on moving the 3-nitro-1,2,4-triazol-1-yl moiety from position 4 to position 2 of the pyrimidine nucleus.
RESUMO
The review provides a summary of synthetic approaches to and medicinal applications of N-aryl-C-nitroazoles. This broad chemical family delivered numerous practical applications in the areas other than pharmaceuticals. This is most likely due to a common stigma associated with nitroheterocycles implying their inherent toxicity. Therefore, the research literature appears to be lacking in medicinal chemistry reports related to this class of compounds. However, despite this notion, the nitroheterocycles have enjoyed a marked renaissance in the last years, particularly, in antimicrobial area. Therefore, an attempt to summarize, within a single review article, the medicinal applications and methods of synthesis has been undertaken.
