The emergence and spread of resistant strains of pathogens as well as reduction of the efficacy of current antimicrobial agents requires the development of novel antimicrobial compounds. The aim of the present study was synthesis and evaluation of antimicrobial activity of new arylaliphatic aminopropanols. The objects of the present study were 1-[4-(1,1,3,3-tetramethylbutyl)phenoxy]-3-dialkylamino-2-propanol quaternary salts (compounds I–XIV). Compounds synthesis was carried out by heating of precursor epoxide and excessive amount of appropriate amines in isopropanole, followed by treatment with excess of alkyl halides. Methods of elemental analysis, IR- and PMR-spectroscopy were used for confirmation of chemical structure. Antimicrobial activity against Staphylococcus аureus АTCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa АТСС 27853 and Candida albicans NCTC 885/653 was determined by a broth dilution method and evaluated via minimum inhibitory concentration (MIC). Our investigation of antibacterial and antifungal activity of 1-[4-(1,1,3,3-tetra methylbutyl)phenoxy]-3-dialkylamino-2-propanol quaternary salts showed that compounds possess narrow spectrum, as well as broad spectrum action. Significant antimicrobial activity of the novel aryl aliphatic aminoalcohols indicates their potential usage as a component of new antimicrobial drugs.

Bacterial biofilm, particularly formed by Pseudomonas aeruginosa, are a cause of severe chronic infectious diseases. Bacteria within a biofilm are phenotypically more resistant to antibiotics and the macroorganism immune system, making it an important virulence factor for many microbes. The aminopropanol derivatives with adamantyl (KVM-97) and N-alkylaryl radicals (KVM-194, KVM-204, KVM-261, and KVM-262) were used as study object. The aim of this study was to investigate the antibiofilm activity of compounds on biofilm formation and on mature biofilm of P. aeruginosa. The effects of the aminopropanol derivatives on the biofilm mass were evaluated by using crystal violet assay. Ciprofloxacin, meropenem, ceftazidime, gentamicin were used as reference substances. Reported results demonstrate that all compounds displayed antibiofilm activity at the tested concentrations. Remarkable reduction in biofilm formation of P. aeruginosa was found after treatment with KVM-97, KVM-261 and KVM-262 in high concentration (5× MIC), biofilm inhibition activity were 84.3%, 90.5% and 83.3% respectively. After a treatment with KVM-204 at 250 μg/ml (5× MIC) 76.6% of the preformed 24-hr biofilms were destroyed. Furthermore, compounds KVM-97, KVM-194, and KVM-261 in both concentrations showed potent antibiofilm activity against the P. aeruginosa, inhibition activity values being between 56.7 and 65.7%. All tested compounds in dose-dependent manner exhibited pronounced inhibition activity against mature 5-days P. аeruginosa biofilm. It was also observed that tested compounds show high antibiofilm activity in comparison to reference antimicrobials. The aminopropanol derivatives may provide templates for a new group of antimicrobial agents and potential future therapeutics for treating chronic infections.

Development of microbial resistance to current antimicrobial drugs created a critical need of the new antiseptics. The object of our study was phenyladamantane derivative (4-(adamantyl-1)-1-(1-aminobutyl)benzol, AM-166). The aim of the presented study was to investigate the specific activity of 4% AM-166 solution in isopropanol and 5% AM-166 solution in 76% ethanol (manufactured by PJSC SIC «Borshchahivskiy CPP») against the wide spectrum of bacteria and fungi, and effective concentrations and exposition time determination. Desinfectant/antiseptic activity was evaluated by quantitative suspension method with subsequent neutralization. Our results showed that both solutions exhibited similar activity against gram-positive and gram-negative bacteria as well as against yeasts. Antibacterial and antifungal action was demonstrated for all investigated concentrations (initial solution, 5-fold and 10-fold dilutions), observed effect was maintained throughout the whole observation period (from 5 to 30 min). Tested solutions in initial concentrations demonstrated fungicidal activity against A. niger. 5-fold dilution of 5% AM-166 solution in 76% ethanol was more effective than 5-fold dilution of 4% AM-166 solution in isopropanol. 10-fold dilutions of both solutions were ineffective against A. niger. The data obtained suggest the prospects of adamantane derivatives for the development of novel antiseptics.

Arylaliphatic aminoalcohols appeared to be the new promising class of compounds for the development of antibacterial and antifungal agents. The aim of the presented study was to analyze the «chemical structure-antimicrobial activity» relationship for further activity-directed synthesis of compounds of this class. The antimicrobial activity of the compounds was investigated by serial broth dilution method. Primary analysis of the effect of substituents’ structure on the ability of the derivatives to inhibit the growth of test-microorganisms was carried out by empirical method. Molecular structural characteristics of arylaliphatic aminoalcohols (surface area, volume, partition coefficient logP and dipole moment) were calculated by means of «Hyperchem 8.0.8» software. Relationship between the antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and molecular characteristics was investigated by correlation analysis using the Spearman test. Statistical processing was performed by «StatSoft Statistica 6.0», the data obtained were evaluated using Chaddock scale. The data obtained suggest, that the presence of both antibacterial and antifungal activity in arylaliphatic aminoalcohols depends on the amino group structure and composition of aryl(alkyl)oxy-radical (4-(1,1,3,3-tetramethylbutyl)phenyl, 1-adamantyl, 4-(1-adamantyl)phenyl, 4-phenyl-phenyl or 2,4-ditretbutyl phenyl). The correlation analysis revealed an inverse relationship between the antimicrobial action and surface area, volume, and lipophilicity of compounds. The tightest correlation was found between these parameters and antistaphylococcal activity. Our results indicate the promises of the synthesis, directed to the reducing of the molecule size and lipophilicity of tetramethylbutylphenyl aminoalcohols, for further development of broad-spectrum antimicrobial agents.

Дослідження виконано в рамках науково-дослідної роботи «Фармакодинамічні аспекти протимікробної активності нових похідних арилаліфатичних аміноспиртів». Реферат. Метою роботи було встановити зміни ультраструктури кишкової палички при дії нового похідного арилаліфатичних аміноспиртів, сполуки КВМ-114. Дослідження проведені з використанням методу трансмісійної електронної мікроскопії. Встановлено, що при інкубації клітин зі сполукою у субінгібуючій концентрації вже через 1 рік спостерігаються порушення структури клітинної оболонки та зміни, що свідчать про пригнічення внутрішньоклітинних процесів.