An amino oxide and three quaternary ammonium salts were investigated for antimicrobial activity. All compounds had low MIC against gram positive bacteria. Despite high MIC the ammonium salts gave good killing of Pseudomonas aeruginosa in time kill experiments. These quaternary ammonium salts may be useful for disinfection as they are easily broken down in the environment.

• MeSH
• Bacteria účinky léků   MeSH
• dezinficiencia farmakologie   MeSH
• dimethylaminy farmakologie   MeSH
• kvartérní amoniové sloučeniny farmakologie   MeSH
• lidé MeSH
• Pseudomonas aeruginosa účinky léků   MeSH
• Staphylococcus aureus účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dezinficiencia MeSH
• dimethylaminy MeSH
• kvartérní amoniové sloučeniny MeSH
• N,N-dimethyl-1-methyldodecylamine oxide MeSH Prohlížeč

Tertiary amines 3-(dialkylamino)-2-hydroxypropyl 4-[(alkoxycarbonyl)amino]benzoates and their quaternary ammonium salts were synthesized. The final step of synthesis of quaternary ammonium salts was carried out by microwave-assisted synthesis. Software-calculated data provided the background needed to compare fifteen new resulting compounds by their physicochemical properties. The acid dissociation constant (pKa) and lipophilicity index (log P) of tertiary amines were determined; while quaternary ammonium salts were characterized by software-calculated lipophilicity index and surface tension. Biological evaluation aimed at testing acetylcholinesterase and butyrylcholinesterase-inhibiting activity of synthesized compounds. A possible mechanism of action of these compounds was determined by molecular modelling study using combined techniques of docking; molecular dynamics simulations and quantum mechanics calculations.

• Klíčová slova
• acetylcholinesterase, arylcarbonyloxyaminopropanols, butyrylcholinesterase, quaternary ammonium salts, tertiary amines,
• MeSH
• acetylcholinesterasa MeSH
• aktivace enzymů účinky léků   MeSH
• benzoáty chemická syntéza   chemie   farmakologie   MeSH
• butyrylcholinesterasa MeSH
• chemické modely MeSH
• cholinesterasové inhibitory chemická syntéza   chemie   farmakologie   MeSH
• kvartérní amoniové sloučeniny chemická syntéza   chemie   farmakologie   MeSH
• molekulární modely * MeSH
• soli chemie   MeSH
• techniky syntetické chemie * MeSH
• vazba proteinů MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• benzoáty MeSH
• butyrylcholinesterasa MeSH
• cholinesterasové inhibitory MeSH
• kvartérní amoniové sloučeniny MeSH
• soli MeSH

• MeSH
• antifungální látky * MeSH
• kvartérní amoniové sloučeniny farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antifungální látky * MeSH
• kvartérní amoniové sloučeniny MeSH

The photothermal cancer therapy using cationic gold nanorods (GNRs) stabilized by quaternary ammonium salts (QAS) have a great potential to enhance conventional cancer treatment as it promises the effective eradication of cancer cells including cells resistant to radio- and chemo-therapy and the stimulation of anti-tumor immune response. However, as the cytotoxicity of the conventional alkanethiol-QAS compounds limits their utility in medicine, here we developed GNRs modified by novel highly hydrophilic cationic surfactant composed of the quaternary ammonium group and ethylene glycol chain N,N,N-trimethyl-3,6,9,12,15-pentaoxaheptadecyl-17-sulfanyl-1-ammonium bromide (POSAB) showing insignificant cytotoxicity in the free state. Surface modification of GNRs by POSAB allowed to prepare nanoparticles with good stability in water, high cellular uptake and localization in lysosomes that are a promising alternative to alkanethiol-stabilized GNRs especially for biomedical applications.

• Klíčová slova
• N,N,N-trimethyl-3,6,9,12,15-pentaoxaheptadecyl-17-sulfanyl-1-ammonium bromide (POSAB), cytotoxicity, gold nanorods, quaternary ammonium salts,
• MeSH
• alkylace MeSH
• CHO buňky MeSH
• Cricetulus MeSH
• hydrofobní a hydrofilní interakce * MeSH
• kvartérní amoniové sloučeniny chemie   MeSH
• nanotrubičky chemie   MeSH
• povrchově aktivní látky chemie   MeSH
• stabilita léku MeSH
• viabilita buněk účinky léků   MeSH
• zlato chemie   toxicita   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kvartérní amoniové sloučeniny MeSH
• povrchově aktivní látky MeSH
• zlato MeSH

Bacterial strains with a high biodegradation potential were isolated from activated sludge. Their ability to decompose the hard bis-quaternary ammonium salt FB was determined by the method of chemical oxygen demand (COD) in a mineral medium, where the compound FB was the only source of carbon. The COD values were very low after 21 d and in the course of this period they reached zero level twice. The contribution of adsorption to decrease the COD value was small. The maximum COD decrease was accompanied by an increase of cell respiration. It is suggested that FB is effectively decomposed in spite of the fact that according to its structure it is a typical hard detergent.

• MeSH
• Bacteria metabolismus   MeSH
• biodegradace * MeSH
• kvartérní amoniové sloučeniny metabolismus   MeSH
• mikrobiologie vody MeSH
• odpadní vody * MeSH
• spotřeba kyslíku MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kvartérní amoniové sloučeniny MeSH
• N,N'-bis(dimethylundecyl)-3-methylaza-1,5-pentanediammonium dibromide MeSH Prohlížeč
• odpadní vody * MeSH

• MeSH
• aminokyseliny metabolismus   MeSH
• antibiotická rezistence genetika   MeSH
• glukosa metabolismus   MeSH
• kvartérní amoniové sloučeniny farmakologie   MeSH
• leucin metabolismus   MeSH
• mikrobiální testy citlivosti MeSH
• mutace účinky léků   MeSH
• prolin metabolismus   MeSH
• Saccharomyces cerevisiae účinky léků   genetika   metabolismus   MeSH
• soli farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminokyseliny MeSH
• glukosa MeSH
• kvartérní amoniové sloučeniny MeSH
• leucin MeSH
• prolin MeSH
• soli MeSH

Since the discovery of antimicrobial agents, the misuse of antibiotics has led to the emergence of bacterial strains resistant to both antibiotics and common disinfectants like quaternary ammonium compounds (QACs). A new class, 'gemini' QACs, which contain two polar heads, has shown promise. Octenidine (OCT), a representative of this group, is effective against resistant microorganisms but has limitations such as low solubility and high cytotoxicity. In this study, we developed 16 novel OCT derivatives. These compounds were subjected to in silico screening to predict their membrane permeation. Testing against nosocomial bacterial strains (G+ and G-) and their biofilms revealed that most compounds were highly effective against G+ bacteria, while compounds 7, 8, and 10-12 were effective against G- bacteria. Notably, compounds 6-8 were significantly more effective than OCT and BAC standards across the bacterial panel. Compound 12 stood out due to its low cytotoxicity and broad-spectrum antimicrobial activity, comparable to OCT. It also demonstrated impressive antifungal activity. Compound 1 was highly selective to fungi and four times more effective than OCT without its cytotoxicity. Several compounds, including 4, 6, 8, 9, 10, and 12, showed strong virucidal activity against murine cytomegalovirus and herpes simplex virus 1. In conclusion, these gemini QACs, especially compound 12, offer a promising alternative to current disinfectants, addressing emerging resistances with their enhanced antimicrobial, antifungal, and virucidal properties.

• Klíčová slova
• Disinfection, Octenidine, Quaternary ammonium salts, Resistance, Synthesis,
• MeSH
• antibakteriální látky * farmakologie   chemická syntéza   chemie   MeSH
• antifungální látky farmakologie   chemická syntéza   chemie   MeSH
• antivirové látky farmakologie   chemická syntéza   chemie   MeSH
• Bacteria účinky léků   MeSH
• biofilmy účinky léků   MeSH
• houby účinky léků   MeSH
• iminy MeSH
• kvartérní amoniové sloučeniny * farmakologie   chemická syntéza   chemie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti * MeSH
• molekulární struktura MeSH
• myši MeSH
• pyridinové sloučeniny farmakologie   chemická syntéza   chemie   MeSH
• pyridiny farmakologie   chemie   chemická syntéza   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• antifungální látky MeSH
• antivirové látky MeSH
• iminy MeSH
• kvartérní amoniové sloučeniny * MeSH
• octenidine MeSH Prohlížeč
• pyridinové sloučeniny MeSH
• pyridiny MeSH

A series of 17 halogenides of quaternary ammonium salts of the alkylpiperidinylethyl esters of 2-pentoxy (and 2-heptoxy) substituted phenylcarbamic acids were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, M. kansasii, and M. avium. Correlation of this action with lipophilicity (log P, 1-octanol-water system) was used for the description of the structure-antimycobacterial activity relationships (QSARs). The activity increased with the increasing lipophilicity of the compounds.

• MeSH
• antibakteriální látky chemie   farmakologie   MeSH
• antituberkulotika farmakologie   MeSH
• fenylkarbamáty chemie   farmakologie   MeSH
• kvantitativní vztahy mezi strukturou a aktivitou MeSH
• kvartérní amoniové sloučeniny chemie   farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• molekulární struktura MeSH
• Mycobacterium avium účinky léků   MeSH
• Mycobacterium kansasii účinky léků   MeSH
• Mycobacterium tuberculosis účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• antituberkulotika MeSH
• fenylkarbamáty MeSH
• kvartérní amoniové sloučeniny MeSH

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

PURPOSE: Plasmonic photothermal cancer therapy by gold nanorods (GNRs) emerges as a promising tool for cancer treatment. The goal of this study was to design cationic oligoethylene glycol (OEG) compounds varying in hydrophobicity and molecular electrostatic potential as ligand shells of GNRs. Three series of ligands with different length of OEG chain (ethylene glycol units = 3, 4, 5) and variants of quaternary ammonium salts (QAS) as terminal functional group were synthesized and compared to a prototypical quaternary ammonium ligand with alkyl chain - (16-mercaptohexadecyl)trimethylammonium bromide (MTAB). METHODS: Step-by-step research approach starting with the preparation of compounds characterized by NMR and HRMS spectra, GNRs ligand exchange evaluation through characterization of cytotoxicity and GNRs cellular uptake was used. A method quantifying the reshaping of GNRs was applied to determine the effect of ligand structure on the heat transport from GNRs under fs-laser irradiation. RESULTS: Fourteen out of 18 synthesized OEG compounds successfully stabilized GNRs in the water. The colloidal stability of prepared GNRs in the cell culture medium decreased with the number of OEG units. In contrast, the cellular uptake of OEG+GNRs by HeLa cells increased with the length of OEG chain while the structure of the QAS group showed a minor role. Compared to MTAB, more hydrophilic OEG compounds exhibited nearly two order of magnitude lower cytotoxicity in free state and provided efficient cellular uptake of GNRs close to the level of MTAB. Regarding photothermal properties, OEG compounds evoked the photothermal reshaping of GNRs at lower peak fluence (14.8 mJ/cm2) of femtosecond laser irradiation than the alkanethiol MTAB. CONCLUSION: OEG+GNRs appear to be optimal for clinical applications with systemic administration of NPs not-requiring irradiation at high laser intensity such as drug delivery and photothermal therapy inducing apoptosis.

• Klíčová slova
• cellular uptake, gold nanorods, oligoethylene glycol, photothermal stability, quaternary ammonium salts,
• MeSH
• biologický transport MeSH
• HeLa buňky MeSH
• hydrofobní a hydrofilní interakce MeSH
• koloidy MeSH
• kvartérní amoniové sloučeniny chemie   MeSH
• lidé MeSH
• ligandy MeSH
• nanotrubičky chemie   MeSH
• polyethylenglykoly chemie   MeSH
• stabilita léku MeSH
• teplota * MeSH
• zlato chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• koloidy MeSH
• kvartérní amoniové sloučeniny MeSH
• ligandy MeSH
• polyethylenglykoly MeSH
• zlato MeSH