Quaternary ammonium salts (QASs) have been widely used for disinfection purposes because of their low price, high efficacy and low human toxicity for decades. However, precise mechanisms of action nor the powerful versatile agent against all antimicrobial species are known. In this study we have prepared 43 novel N-alkyl monoquaternary ammonium salts including 7 N,N-dialkyl monoquaternary ammonium salts differing bearing alkyl chain either of 12, 14 or 16 carbons. Together with 15 already published QASs we have studied the antimicrobial efficacy of all water-soluble compounds together with standard benzalkonium salts against Gram-positive (G+) and Gram-negative (G-) bacteria, anaerobic spore-forming Cl. difficile, yeasts, filamentous fungi and enveloped Varicella zoster virus (VZV). To address the mechanism of action, lipophilicity seems to be a key parameter which determines antimicrobial efficacy, however, exceptions are likely to occur and therefore QSAR analysis on the efficacy against G+ and G- bacteria was applied. We showed that antibacterial activity is higher when the molecule is larger, more lipophilic, less polar, and contains fewer oxygen atoms, fewer methyl groups bound to heteroatoms or fewer hydrogen atoms bound to polarized carbon atoms. In addition, from an application point of view, we have formulated mixtures, on the basis of obtained efficiency of individual compounds, in order to receive wide-spectrum agent. All formulated mixtures completely eradicated tested G+ and G- strains, including the multidrug-resistant P. aeruginosa as well as in case of yeasts. However, effect on A. fumigatus, Cl. difficile and VZV the exposition towards mixture resulted in significant reduction only. Finally, 3 out of 4 formulated mixtures were safer than reference commercial agent based on benzalkonium salts only in the skin irritation test using reconstructed human epidermidis.
- Klíčová slova
- Antimicrobial activity, Bacteria, Cytotoxicity, Fungi, Mixtures, Quaternary ammonium salts, Virus,
- MeSH
- alkylace MeSH
- antiinfekční látky škodlivé účinky chemie farmakologie MeSH
- kůže účinky léků MeSH
- kvantitativní vztahy mezi strukturou a aktivitou * MeSH
- kvartérní amoniové sloučeniny škodlivé účinky chemie farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiinfekční látky MeSH
- kvartérní amoniové sloučeniny MeSH
The aim of the cohort retrospective study was to analyze and evaluate the influence of certain factors (age, profession, smoking) on the characteristics and the incidence rate of the upper respiratory tract diseases (URTDs) in the occupational contact with ammonium. Subjects were 180 men, divided into 3 professional groups. The average shift concentrations of ammonium were measured in the permanent work places and individually by personal passive dosemeters. The URTDs were classified into 15 groups according to localization and the stage of the inflammatory process. The relationships "time-response" and "dose (concentration)-response" were determined. The factor "cumulative exposure" was used in order to evaluate the actual noxious effect of NH3 on the mucose of the upper respiratory tract (URT). There was a statistically reliable difference found in the incidence rate of atrophic rhinitis, hypertrophic pharyngitis and laryngitis, and neoplasms of the URT in the workers with the highest cumulative exposure. For this group relative risk was 4.00, 2.22, 3.20 and 4.00, respectively, with 95% Cl. The "cumulative exposure" factor gives the best proofs for the toxic effect of ammonium and a possibility for assessment of the relative risk.
- MeSH
- dospělí MeSH
- hodnocení rizik MeSH
- infekce dýchací soustavy chemicky indukované epidemiologie MeSH
- kohortové studie MeSH
- kvartérní amoniové sloučeniny škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory dýchací soustavy chemicky indukované epidemiologie MeSH
- nemoci z povolání chemicky indukované epidemiologie MeSH
- retrospektivní studie MeSH
- sběr dat MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Bulharsko epidemiologie MeSH
- Názvy látek
- kvartérní amoniové sloučeniny MeSH
