Pattern 1-hydroxy-N-(2,4,5-trichlorophenyl)-2-naphthamide and the thirteen original carbamates derived from it were prepared and characterized. All the compounds were tested against Staphylococcus aureus ATCC 29213 as a reference and quality control strain and in addition against three clinical isolates of methicillin-resistant S. aureus (MRSA). Moreover, the compounds were evaluated against Enterococcus faecalis ATCC 29212, and preliminary in vitro cytotoxicity of the compounds was assessed using the human monocytic leukemia cell line (THP-1). The lipophilicity of the prepared compounds was experimentally determined and correlated with biological activity. While pattern anilide had no antibacterial activity, the prepared carbamates demonstrated high antistaphylococcal activity comparable to the used standards (ampicillin and ciprofloxacin), which unfortunately were ineffective against E. feacalis. 2-[(2,4,5-Trichlorophenyl)carba- moyl]naphthalen-1-yl ethylcarbamate (2) and 2-[(2,4,5-trichlorophenyl)carbamoyl]naphthalen-1-yl butylcarbamate (4) expressed the nanomolar minimum inhibitory concentrations (MICs 0.018−0.064 μM) against S. aureus and at least two other MRSA isolates. Microbicidal effects based on the minimum bactericidal concentrations (MBCs) against all the tested staphylococci were found for nine carbamates, while 2-[(2,4,5-trichlorophenyl)carbamoyl]naphthalen-1-yl heptylcarbamate (7) and 2-[(2,4,5-trichlorophenyl)carbamoyl]naphthalen-1-yl (4-phenylbutyl)carbamate (14) demonstrated MBCs in the range of 0.124−0.461 μM. The selectivity index (SI) for most investigated carbamates was >20 and for some derivatives even >100. The performed tests did not show an effect on the damage to the bacterial membrane, while the compounds were able to inhibit the respiratory chain of S. aureus.

• Klíčová slova
• antistaphylococcal activity, carbamates, cytotoxicity, hydroxynaphthalenes, lipophilicity, structure–activity relationships,
• Publikační typ
• časopisecké články MeSH

A series of N-alkyl-3-(alkylamino)pyrazine-2-carboxamides and their N-alkyl-3-chloropyrazine-2-carboxamide precursors were prepared. All compounds were characterized by analytical methods and tested for antimicrobial and antiviral activity. The antimycobacterial MIC values against Mycobacterium tuberculosis H37Rv of the most effective compounds, 3-(hexylamino)-, 3-(heptylamino)- and 3-(octylamino)-N-methyl-pyrazine-2-carboxamides 14‒16, was 25 μg/mL. The compounds inhibited photosystem 2 photosynthetic electron transport (PET) in spinach chloroplasts. This activity was strongly connected with the lipophilicity of the compounds. For effective PET inhibition longer alkyl chains in the 3-(alkylamino) substituent in the N-alkyl-3-(alkylamino)pyrazine-2-carboxamide molecule were more favourable than two shorter alkyl chains.

• Klíčová slova
• alkylation, aminodehalogenation, antimycobacterial activity, inhibition of photosynthetic electron transport, pyrazinamide, pyrazine, structure-activity relationships,
• MeSH
• antituberkulotika chemická syntéza   farmakologie   MeSH
• bakteriální proteiny antagonisté a inhibitory   metabolismus   MeSH
• chloroplasty metabolismus   MeSH
• mikrobiální testy citlivosti MeSH
• Mycobacterium tuberculosis účinky léků   metabolismus   MeSH
• pyrazinamid chemická syntéza   chemie   farmakologie   MeSH
• pyraziny chemická syntéza   farmakologie   MeSH
• Spinacia oleracea metabolismus   MeSH
• syntázy mastných kyselin antagonisté a inhibitory   metabolismus   MeSH
• transport elektronů účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antituberkulotika MeSH
• bakteriální proteiny MeSH
• fatty acid synthase I, mycobacteria MeSH Prohlížeč
• pyrazinamid MeSH
• pyraziny MeSH
• syntázy mastných kyselin MeSH

The effect of the newly synthesized phosphonic compound dibutyl 2-octylamino-2-propanephosphonate (DBOP) on the growth of the aquatic plant Spirodela oligorrhiza and stability of red blood cells (RBC) and planar lipid membranes (BLM) was studied to determine its physiological activity and, if possible, correlate this activity to compound-induced changes in the mechanical properties of the model membranes. The measure of the phytotoxicity was the DBOP concentration causing 50% plant growth retardation, while measures of stability of model membranes were 100% hemolysis of RBC and a critical concentration of DBOP causing BLM destruction in no more that 3 min. These data were compared with those for dibutyl 1-butylamino-1-cyclohexanephosphonate (DBBC) and diethyl 9-butylamino-9-fluorenephosphonate (DEBF) known for their physiological activities. Both DBBC and DEBF influenced Spirodela growth significantly less than DBOP Destabilization of the model membrane caused by DBBC and DBOP was similar whereas DEBF exerted a weak influence on RBC and BLM stability. The results indicate that the physiological activities of DBOP and DEBF are not limited to the lipid phase of biological membranes and may involve also disturbance of metabolic processes.

• MeSH
• buněčná membrána účinky léků   MeSH
• erytrocyty účinky léků   MeSH
• hemolýza MeSH
• lipidové dvojvrstvy chemie   MeSH
• listy rostlin účinky léků   fyziologie   MeSH
• organofosforové sloučeniny farmakologie   MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lipidové dvojvrstvy MeSH
• organofosforové sloučeniny MeSH

Antipseudomonadal activity of homologous series of six quaternary bisammonium salts (QBAS) (4,7-dioxo-3,8-dioxadekan-1,1-[bis(alkyldimethyldiammonium dibromide)] as well as the effect of their subinhibitory concentrations (sub-MICs) on Pseudomonas aeruginosa virulence factors was studied. Antibacterial activity of QBAS increased up to a certain length of the chain and then decreased with further elongation. All the tested sub-MICs of QBAS caused a significant suppression of phospholipase C activity (to 0-41%). Elastase and proteinase activity were less efficiently reduced. A more effective decrease of these activities was only found after treatment with one-fourth of the MICs of the tested substances. QBAS caused only an erratic decrease of alginate production.

• MeSH
• algináty metabolismus   MeSH
• antibakteriální látky chemie   farmakologie   MeSH
• fosfolipasy typu C antagonisté a inhibitory   MeSH
• inhibitory enzymů chemie   farmakologie   MeSH
• inhibitory proteas chemie   farmakologie   MeSH
• kvartérní amoniové sloučeniny chemie   farmakologie   MeSH
• kyselina glukuronová MeSH
• kyseliny hexuronové MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• molekulární struktura MeSH
• pankreatická elastasa antagonisté a inhibitory   MeSH
• Pseudomonas aeruginosa účinky léků   metabolismus   patogenita   MeSH
• virulence účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• algináty MeSH
• antibakteriální látky MeSH
• fosfolipasy typu C MeSH
• inhibitory enzymů MeSH
• inhibitory proteas MeSH
• kvartérní amoniové sloučeniny MeSH
• kyselina glukuronová MeSH
• kyseliny hexuronové MeSH
• pankreatická elastasa MeSH

New surface-active bisquaternary ammonium salts derived from bis-(2-dimethylaminoethyl) ester of glutaric acid are highly effective against representatives of Gram-positive, Gram-negative bacteria and yeasts. Relationships between structure, lipophilicity and antimicrobial effectiveness were demonstrated by quantitative structure-activity methodology. The non-linear dependence of biological activity on the structure as well as lipophilicity (expressed as critical micelle concentration-CMC) was shown using Kubinyi's bilinear model. The most effective compounds were those with the alkyl chain of 11-12 carbon atoms and with the CMC values around 0.7-1.0 mmol/L. These derivatives possessed higher antimicrobial activity particularly to Gram-negative bacteria.

• MeSH
• antibakteriální látky MeSH
• antifungální látky chemická syntéza   farmakologie   MeSH
• antiinfekční látky chemická syntéza   farmakologie   MeSH
• Candida albicans účinky léků   MeSH
• Escherichia coli účinky léků   MeSH
• kvartérní amoniové sloučeniny farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• povrchově aktivní látky farmakologie   MeSH
• Staphylococcus aureus účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• antifungální látky MeSH
• antiinfekční látky MeSH
• kvartérní amoniové sloučeniny MeSH
• povrchově aktivní látky MeSH