Antimycobacterial Activity of Quaternary Pyridinium Salts and Pyridinium N-oxides - Review

Martin      Kratky; Jarmila      Vinsova

Abstract

The treatment of tuberculosis and other mycobacterioses is still a major world health problem and new antimycobacterial compounds unrelated to approved drugs are in demand. Quaternary ammonium salts have revealed many usable properties especially as antimicrobials; they are widely used as disinfection and antiseptic agents. Some of these compounds, including pyridinium salts, have revealed substantial antimycobacterial action, although the presence of the cationic nitrogen itself is not sufficient for activity. A long Nalkyl chain is also not necessary for antimycobacterial activity, although it is associated with improved activity.

Compounds that have shown significant in vitro activity, e.g., cetylpyridinium, N-(substituted alkyl)pyridinium salts, 3-[(5- cyclopentylpentyl)(substituted phenyl)amino]-1-methylpyridinium iodides or pyridinium alkyl ethers of steroids (good activity with minimum inhibitory concentrations – MIC from 0.4 μg/mL). However, most pyridinium salts have mild or moderate activity against fastand/ or slow-growing mycobacteria, including N-methylated isoniazids or pyridinium-based oximes. Moreover, a pyridinium ring is present in some cefalosporines (e.g., cefaloridine, ceftazidime and cefsulodine) with antimycobacterial properties. The N-oxidation of pyridine mostly resulted in retained or increased minimum inhibitory concentrations. Additionally, the action of pyridinium N-oxides against mycobacteria is not especially robust.

The mechanism of action of pyridinium compounds remains elusive, but the inhibition of some mycobacterial enzymes has been described for a few derivatives.

Keywords: Antimicrobial activity, mycobacteria, pyridinium N-oxides, pyridinium salts, quaternary ammonium salts, tuberculosis, mycobacterioses, cetylpyridinium, minimum inhibitory concentrations, derivatives