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.

• Keywords
• antistaphylococcal activity, carbamates, cytotoxicity, hydroxynaphthalenes, lipophilicity, structure–activity relationships,
• Publication type
• Journal Article 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.

• Keywords
• alkylation, aminodehalogenation, antimycobacterial activity, inhibition of photosynthetic electron transport, pyrazinamide, pyrazine, structure-activity relationships,
• MeSH
• Antitubercular Agents chemical synthesis   pharmacology   MeSH
• Bacterial Proteins antagonists & inhibitors   metabolism   MeSH
• Chloroplasts metabolism   MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium tuberculosis drug effects   metabolism   MeSH
• Pyrazinamide chemical synthesis   chemistry   pharmacology   MeSH
• Pyrazines chemical synthesis   pharmacology   MeSH
• Spinacia oleracea metabolism   MeSH
• Fatty Acid Synthases antagonists & inhibitors   metabolism   MeSH
• Electron Transport drug effects   MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antitubercular Agents MeSH
• Bacterial Proteins MeSH
• fatty acid synthase I, mycobacteria MeSH Browser
• Pyrazinamide MeSH
• Pyrazines MeSH
• Fatty Acid Synthases 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
• Cell Membrane drug effects   MeSH
• Erythrocytes drug effects   MeSH
• Hemolysis MeSH
• Lipid Bilayers chemistry   MeSH
• Plant Leaves drug effects   physiology   MeSH
• Organophosphorus Compounds pharmacology   MeSH
• Swine MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Lipid Bilayers MeSH
• Organophosphorus Compounds 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
• Alginates metabolism   MeSH
• Anti-Bacterial Agents chemistry   pharmacology   MeSH
• Type C Phospholipases antagonists & inhibitors   MeSH
• Enzyme Inhibitors chemistry   pharmacology   MeSH
• Protease Inhibitors chemistry   pharmacology   MeSH
• Quaternary Ammonium Compounds chemistry   pharmacology   MeSH
• Glucuronic Acid MeSH
• Hexuronic Acids MeSH
• Humans MeSH
• Microbial Sensitivity Tests MeSH
• Molecular Structure MeSH
• Pancreatic Elastase antagonists & inhibitors   MeSH
• Pseudomonas aeruginosa drug effects   metabolism   pathogenicity   MeSH
• Virulence drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Alginates MeSH
• Anti-Bacterial Agents MeSH
• Type C Phospholipases MeSH
• Enzyme Inhibitors MeSH
• Protease Inhibitors MeSH
• Quaternary Ammonium Compounds MeSH
• Glucuronic Acid MeSH
• Hexuronic Acids MeSH
• Pancreatic Elastase 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
• Anti-Bacterial Agents MeSH
• Antifungal Agents chemical synthesis   pharmacology   MeSH
• Anti-Infective Agents chemical synthesis   pharmacology   MeSH
• Candida albicans drug effects   MeSH
• Escherichia coli drug effects   MeSH
• Quaternary Ammonium Compounds pharmacology   MeSH
• Microbial Sensitivity Tests MeSH
• Surface-Active Agents pharmacology   MeSH
• Staphylococcus aureus drug effects   MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Antifungal Agents MeSH
• Anti-Infective Agents MeSH
• Quaternary Ammonium Compounds MeSH
• Surface-Active Agents MeSH