Wide-Antimicrobial Spectrum of Picolinium Salts

Abstract

Nosocomial infections, which greatly increase morbidity among hospitalized patients, together with growing antibiotic resistance still encourage many researchers to search for novel antimicrobial compounds. Picolinium salts with different lengths of alkyl chains (C₁₂, C₁₄, C₁₆) were prepared by Menshutkin-like reaction and evaluated with respect to their biological activity, i.e., lipophilicity and critical micellar concentration. Picolinium salts with C₁₄ and C₁₆ side chains achieved similar or even better results when in terms of antimicrobial efficacy than benzalkoniums; notably, their fungicidal efficiency was substantially more potent. The position of the methyl substituent on the aromatic ring does not seem to affect antimicrobial activity, in contrast to the effect of length of the N-alkyl chain. Concurrently, picolinium salts exhibited satisfactory low cytotoxicity against mammalian cells, i.e., lower than that of benzalkonium compounds, which are considered as safe.

Keywords: antimicrobial activity; critical micellar concentration; cytotoxicity; picolinium salts; quaternary ammonium compounds; surfactant.

Figure 1

Cidal effect of QAS. Disintegration mechanism of the membrane by QAS attachment on to the membrane, followed by incorporation of side chains into the membrane resulting in membrane rupture and cytosol leakage (A). Fundamental composition of cell walls (B).

Scheme 1

Preparation of alkyl chain compounds; n = 5, 6, 7; R = CH₃.

Figure 2

Correlation between compound structure and physicochemical properties. Graphs show the lipophilicity of the prepared compounds and their dependency on chain elongation (A). Stauff-Klevens plots of log CMC and extended chain of surfactants (B).

Figure 3

The biological assessment of prepared picolinium salts 4a–6c. Minimum inhibitory concentration (MIC) after 24 h or 48 h incubation against Gram-positive (A or C) and Gram-negative bacteria (B or D). Minimum bactericidal concentration (MBC) after 48 h treatment against Gram-positive (E) and Gram-negative bacteria (F). Minimum inhibitory concentrations (MIC) determined on a panel of four yeasts and three filamentous fungi after 72 h (yeasts)/168 h (filamentous fungi) incubation (G). Virucidal efficacy against varicella zoster virus (VZV); 5 min exposure to 0.01%; or 0.005%; expressed as ΔTCID₅₀ (H). Complete data are listed in Tables S1, S2 and S3.

Figure 4

Cytotoxicity of prepared QASs 4a–6c (A) and their comparison with benzalkonium salts 4–6B (B).