scholarly journals Sterically Hindered Quaternary Phosphonium Salts (QPSs): Antimicrobial Activity and Hemolytic and Cytotoxic Properties

2021 ◽  
Vol 23 (1) ◽  
pp. 86
Author(s):  
Vadim V. Ermolaev ◽  
Daria M. Arkhipova ◽  
Vasili A. Miluykov ◽  
Anna P. Lyubina ◽  
Syumbelya K. Amerhanova ◽  
...  

Structure–activity relationships are important for the design of biocides and sanitizers. During the spread of resistant strains of pathogenic microbes, insights into the correlation between structure and activity become especially significant. The most commonly used biocides are nitrogen-containing compounds; the phosphorus-containing ones have been studied to a lesser extent. In the present study, a broad range of sterically hindered quaternary phosphonium salts (QPSs) based on tri-tert-butylphosphine was tested for their activity against Gram-positive (Staphylococcus aureus, Bacillus сereus, Enterococcus faecalis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and fungi (Candida albicans, Trichophyton mentagrophytes var. gypseum). The cation structure was confirmed to determine their biological activity. A number of QPSs not only exhibit high activity against both Gram-positive and -negative bacteria but also possess antifungal properties. Additionally, the hemolytic and cytotoxic properties of QPSs were determined using blood and a normal liver cell line, respectively. The results show that tri-tert-butyl(n-dodecyl)phosphonium and tri-tert-butyl(n-tridecyl)phosphonium bromides exhibit both low cytotoxicity against normal human cells and high antimicrobial activity against bacteria, including methicillin-resistant strains S. aureus (MRSA). The mechanism of QPS action on microbes is discussed. Due to their high selectivity for pathogens, sterically hindered QPSs could serve as effective tunable biocides.


2012 ◽  
Vol 48 (12) ◽  
pp. 1576-1577 ◽  
Author(s):  
V. V. Andriyashin ◽  
Yu. V. Bakhtiyarova ◽  
R. A. Cherkasov ◽  
V. I. Galkin ◽  
I. V. Galkina


ChemInform ◽  
2013 ◽  
Vol 44 (21) ◽  
pp. no-no
Author(s):  
V. V. Andriyashin ◽  
Yu. V. Bakhtiyarova ◽  
R. A. Cherkasov ◽  
V. I. Galkin ◽  
I. V. Galkina


2012 ◽  
Vol 48 (12) ◽  
pp. 1574-1575 ◽  
Author(s):  
V. V. Andriyashin ◽  
Yu. V. Bakhtiyarova ◽  
R. A. Cherkasov ◽  
V. I. Galkin ◽  
I. V. Galkina


2020 ◽  
Vol 13 (11) ◽  
pp. 375
Author(s):  
Surendra Babu Lagu ◽  
Rajendra Prasad Yejella ◽  
Richie R. Bhandare ◽  
Afzal B. Shaik

Despite the availability of many drugs to treat infectious diseases, the problems like narrow antimicrobial spectrum, drug resistance, hypersensitivities and systemic toxicities are hampering their clinical utility. Based on the above facts, in the present study, we designed, synthesized and evaluated the antibacterial and antifungal activity of novel fluorinated compounds comprising of chalcones bearing trifluoromethyl (A1–A10) and trifluoromethoxy (B1–B10) substituents. The compounds were characterized by spectroscopic techniques and evaluated for their antimicrobial activity against four pathogenic Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Escherichia coli and Bacillus subtilis) bacterial and fungal (Candida albicans and Aspergillus niger) strains. In this study, the compounds with trifluoromethoxy group were more effective than those with trifluoromethyl group. Among the 20 fluorinated chalcones, compound A3/B3 bearing an indole ring attached to the olefinic carbon have been proved to possess the most antimicrobial activity compared to the standard drugs without showing cytotoxicity on human normal liver cell line (L02). Further, the minimum inhibitory concentration (MIC) for A3/B3 was determined by serial tube dilution method and showed potential activity. These results would provide promising access to future study about the development of novel agents against bacterial and fungal infections.



Author(s):  
О.В. Шамова ◽  
М.С. Жаркова ◽  
П.М. Копейкин ◽  
Д.С. Орлов ◽  
Е.А. Корнева

Антимикробные пептиды (АМП) системы врожденного иммунитета - соединения, играющие важную роль в патогенезе инфекционных заболеваний, так как обладают свойством инактивировать широкий спектр патогенных бактерий, обеспечивая противомикробную защиту живых организмов. В настоящее время АМП рассматриваются как потенциальные соединения-корректоры инфекционной патологии, вызываемой антибиотикорезистентными бактериями (АБР). Цель данной работы состояла в изученим механизмов антибактериального действия трех пептидов, принадлежащих к семейству бактенецинов - ChBac3.4, ChBac5 и mini-ChBac7.5Nb. Эти химически синтезированные пептиды являются аналогами природных пролин-богатых АМП, обнаруженных в лейкоцитах домашней козы Capra hircus и проявляющих высокую антимикробную активность, в том числе и в отношении грамотрицательных АБР. Методы. Минимальные ингибирующие и минимальные бактерицидные концентрации пептидов (МИК и МБК) определяли методом серийных разведений в жидкой питательной среде с последующим высевом на плотную питательную среду. Эффекты пептидов на проницаемость цитоплазматической мембраны бактерий для хромогенного маркера исследовали с использованием генетически модифицированного штамма Escherichia coli ML35p. Действие бактенецинов на метаболическую активность бактерий изучали с применением маркера резазурина. Результаты. Показано, что все исследованные пептиды проявляют высокую антимикробную активность в отношении Escherichia coli ML35p и антибиотикоустойчивых штаммов Escherichia coli ESBL и Acinetobacter baumannii in vitro, но их действие на бактериальные клетки разное. Использован комплекс методик, позволяющих наблюдать в режиме реального времени динамику действия бактенецинов в различных концентрациях (включая их МИК и МБК) на барьерную функцию цитоплазматической мембраны и на интенсивность метаболизма бактериальных клеток, что дало возможность выявить различия в характере воздействия бактенецинов, отличающихся по структуре молекулы, на исследуемые микроорганизмы. Установлено, что действие каждого из трех исследованных бактенецинов в бактерицидных концентрациях отличается по эффективности нарушения целостности бактериальных мембран и в скорости подавления метаболизма клеток. Заключение. Полученная информация дополнит существующие фундаментальные представления о механизмах действия пролин-богатых пептидов врожденного иммунитета, а также послужит основой для биотехнологических исследований, направленных на разработку на базе этих соединений новых антибиотических препаратов для коррекции инфекционных заболеваний, вызываемых АБР и являющимися причинами тяжелых внутрибольничных инфекций. Antimicrobial peptides (AMPs) of the innate immunity are compounds that play an important role in pathogenesis of infectious diseases due to their ability to inactivate a broad array of pathogenic bacteria, thereby providing anti-microbial host defense. AMPs are currently considered promising compounds for treatment of infectious diseases caused by antibiotic-resistant bacteria. The aim of this study was to investigate molecular mechanisms of the antibacterial action of three peptides from the bactenecin family, ChBac3.4, ChBac5, and mini-ChBac7.5Nb. These chemically synthesized peptides are analogues of natural proline-rich AMPs previously discovered by the authors of the present study in leukocytes of the domestic goat, Capra hircus. These peptides exhibit a high antimicrobial activity, in particular, against antibiotic-resistant gram-negative bacteria. Methods. Minimum inhibitory and minimum bactericidal concentrations of the peptides (MIC and MBC) were determined using the broth microdilution assay followed by subculturing on agar plates. Effects of the AMPs on bacterial cytoplasmic membrane permeability for a chromogenic marker were explored using a genetically modified strain, Escherichia coli ML35p. The effect of bactenecins on bacterial metabolic activity was studied using a resazurin marker. Results. All the studied peptides showed a high in vitro antimicrobial activity against Escherichia coli ML35p and antibiotic-resistant strains, Escherichia coli ESBL and Acinetobacter baumannii, but differed in features of their action on bacterial cells. The used combination of techniques allowed the real-time monitoring of effects of bactenecin at different concentrations (including their MIC and MBC) on the cell membrane barrier function and metabolic activity of bacteria. The differences in effects of these three structurally different bactenecins on the studied microorganisms implied that these peptides at bactericidal concentrations differed in their capability for disintegrating bacterial cell membranes and rate of inhibiting bacterial metabolism. Conclusion. The obtained information will supplement the existing basic concepts on mechanisms involved in effects of proline-rich peptides of the innate immunity. This information will also stimulate biotechnological research aimed at development of new antibiotics for treatment of infectious diseases, such as severe in-hospital infections, caused by antibiotic-resistant strains.



2020 ◽  
Author(s):  
Nusrat Abedin ◽  
Abdullah Hamed A Alshehri ◽  
Ali M A Almughrbi ◽  
Olivia Moore ◽  
Sheikh Alyza ◽  
...  

Antimicrobial resistance (AMR) has become one of the more serious threats to the global health. The emergence of bacteria resistant to antimicrobial substances decreases the potencies of current antibiotics. Consequently, there is an urgent and growing need for the developing of new classes of antibiotics. Three prepared novel iron complexes have a broad-spectrum antimicrobial activity with minimum bactericidal concentration (MBC) values ranging from 3.5 to 10 mM and 3.5 to 40 mM against Gram-positive and Gram-negative bacteria with antimicrobial resistance phenotype, respectively. Time-kill studies and quantification of the extracellular DNA confirmed the bacteriolytic mode of action of the iron-halide compounds. Additionally, the novel complexes showed significant antibiofilm activity against the tested pathogenic bacterial strains at concentrations lower than the MBC. The cytotoxic effect of the complexes on different mammalian cell lines show sub-cytotoxic values at concentrations lower than the minimum bactericidal concentrations.



2018 ◽  
Vol 22 (2) ◽  
pp. 311-317
Author(s):  
O.A. Nazarchuk ◽  
A.I. Starodub ◽  
O.V. Rymsha ◽  
V.A. Starodub ◽  
S.A. Kolodii

The study of the etiological structure, the properties of pathogens of the respiratory infectious diseases in children and their resistance to antibacterial agents is particularly relevant in modern conditions, expands the search for new approaches to combating pathogens, improves the results of treatment and reduces the mortality of this pathology. The aim — study of etiological structure, sensitivity to antibiotics and antiseptics of pathogens of infectious and inflammatory diseases of respiratory organs in children. In the study there were enrolled 247 patients who were treated in Vinnytsia Regional Children’s Clinical Hospital (VRCCH) in 2016. The sensitivity of microorganisms to 23 antibacterial agents was determined by the disc-diffusion method according to the generally accepted method. The analysis of the antimicrobial activity of antiseptic drugs (decamethoxine, miramistin, chlorhexidine digluconate) was performed by a double serial dilution technique with the determination of the minimum inhibitory bacteriostatic (MIC) and bactericidal (MBcC) concentrations, by the method of successive serial dilutions of the drug in a liquid nutrient medium. In patients who were in inpatient treatment at the VRCCH in 2016 because of pneumonia there were found opportunistic microorganisms which were of etiological significance in the development of the infection. Among them there were Streptococci (47,3 %), Staphylococci (15,3 %), Candida (13,3 %), Enterococci (10,9 %), including a high proportion of owned non-fermenting gram negative bacilli (9,8%) and species of Enterobacteria (2,0 %). Isolated strains of microorganisms had moderate resistance to most modern antibiotic drugs. The sensitivity of isolated strains of microorganisms to reserved antibiotics as carbapenems, often being used in the treatment of critical states of patients in the intensive care units, was found to above 18,2%. The sensitivity to this antibiotic in Enterococcus spp. (7,1 %), Staphylococcus spp. (5,9 %) was also low. Carbapenems, fluoroquinolones (the 1st and 2nd generations), antibiotics and aminoglycosides were found to be effective against gram positive microorganisms in more then 45% of cases. According to this they were considered to be as drugs of choice in the treatment of infectious and purulent-inflammatory pathology of respiratory organs, caused metitcilin- and vancomycin-resistant strains of microorganisms. Resistance to these drugs among investigated strains did not exceed 9,0 %. The high bactericidal properties of antiseptics as decamethoxine was determined against S.pyogenes, Staphylococcus spp. Its MBcC against these bacteria (1,65±0,20 mkg/ml and 4,32±0,50 mkg/ml, respectively) proved the advantage of decamethoxine’s effectiveness in comparison with chlorhexidine digluconate 3,14 times, 2,44 times miramistin. Clinical strains of C.albicans showed the highest susceptibility to decamethoxine, which fungicidal activity was determined in the presence (16,17±2,33 mkg/ml), in comparison with chlorxedine (MFtsK 27,59±3,59 mg/ml) and miramistin activity (27,59±3,595 mkg/ml). In children with inflammatory diseases of the respiratory organs gram-positive cocci are among the predominant pathogens (73,5 %) of cases, in the association allocated – 8,0 % of pathogens. Allocated strains of microorganisms were moderately resistant to all antibiotics studied. For antimicrobial activity antiseptic drugs, especially decamethoxine, have advantages over antibiotics confirming the possibility of their use in combination with systemic antibacterials.



2016 ◽  
pp. 404
Author(s):  
بهاء عبدالله لفتة الربيعى ◽  
هند حسين عبيد ◽  
تحرير هادى صالح




2020 ◽  
Vol 22 (1) ◽  
pp. 105
Author(s):  
Wanting Li ◽  
Zixuan Huang ◽  
Rui Cai ◽  
Wan Yang ◽  
Huawei He ◽  
...  

Silver-based hybrid nanomaterials are receiving increasing attention as potential alternatives for traditional antimicrobial agents. Here, we proposed a simple and eco-friendly strategy to efficiently assemble zinc oxide nanoparticles (ZnO) and silver nanoparticles (AgNPs) on sericin-agarose composite film to impart superior antimicrobial activity. Based on a layer-by-layer self-assembly strategy, AgNPs and ZnO were immobilized on sericin-agarose films using the adhesion property of polydopamine. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray powder diffraction spectroscopy were used to show the morphology of AgNPs and ZnO on the surface of the composite film and analyze the composition and structure of AgNPs and ZnO, respectively. Water contact angle, swelling ratio, and mechanical property were determined to characterize the hydrophilicity, water absorption ability, and mechanical properties of the composite films. In addition, the antibacterial activity of the composite film was evaluated against Gram-positive and Gram-negative bacteria. The results showed that the composite film not only has desirable hydrophilicity, high water absorption ability, and favorable mechanical properties but also exhibits excellent antimicrobial activity against both Gram-positive and Gram-negative bacteria. It has shown great potential as a novel antimicrobial biomaterial for wound dressing, artificial skin, and tissue engineering.



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