New piperidinium surfactants with carbamate fragments as effective adjuvants in insecticide compositions based on imidacloprid.

BACKGROUND: Surfactants, particularly non-ionic ones, are widely used as adjuvants in pesticide formulations due to their ability to maintain pesticide effectiveness without changing solution properties, such as pH. While non-ionic surfactants are generally low-toxic, stable, and excellent dispersants with high solubilization capabilities, they may be less effective than cationic surfactants, which offer superior surface activity, transport properties, and antimicrobial action. This study investigates the efficacy of new piperidinium surfactants with carbamate fragments as adjuvants in insecticide formulations containing imidacloprid. The efficacy of these formulations is being assessed against greenhouse whitefly, a pest known to harm cultivated and ornamental flowering plants. RESULTS: The aggregation behavior of piperidinium surfactants containing carbamate fragments was investigated, and their wetting effect was evaluated. Synthesized surfactants have lower CMC values compared to their methylpiperidinium analogue. The effect of piperidinium surfactants on the insecticide concentration on the surface and inside tomato leaves was assessed using spectrophotometric methods. It was found that the introduction of piperidinium surfactants with carbamate fragment at a concentration of 0.1% wt. allows for decrease in lethal concentration of imidacloprid up to 10 times, thereby testifying the marked increase in the effectiveness of imidacloprid against the greenhouse whitefly insect pest (Trialeurodes vaporariorum). It was shown that the main factors responsible for the enhanced efficacy of the insecticide were the ability of the surfactant to increase the concentration of imidacloprid on the leaf surfaces and improve their penetration into the plant. CONCLUSION: The presented work employed a comprehensive approach, which significantly increases the generalizability of the results obtained and provides the ability to predict the effect and target selection of adjuvants. © 2024 Society of Chemical Industry.

Piperidinium surfactants functionalized with carbamate fragment: Aggregation, antimicrobial activity and cytotoxicity.

The biomimetic nature of supramolecular systems, the structural similarity of synthetic surfactants to biomolecules (lipids, proteins), provide them with high membranotropy, the ability to overcome biological barriers, and affinity towards biosubstances. Despite rather high toxicity cationic surfactants are of importance as antimicrobial agents, gene nanocarriers and mitochondria targeted ligands. To minimize this limitation, cationic amphiphilic matrix undergoes modification with various functional groups. In this work, new piperidinium cationic surfactants containing one or two carbamate fragments were prepared; their aggregation behavior was systematically studied by tensiometery, spectrophotometry and fluorimetry. The presence of a carbamate fragment leads to a 2-3-fold decrease in critical micelle concentration and to a significant increase in solubilization capacity compared to unsubstituted analogue. Evaluation of the antimicrobial effect showed that all compounds exhibit high bactericidal and fungicidal activity against a wide range of pathogenic microorganisms, including their resistant forms. Importantly, the introducing carbamate moiety allows of decreasing hemolytic activity of cationic surfactants. The data obtained make it possible to recommend carbamate piperidinium surfactants as effective biocompatible and biodegradable nanocontainers for hydrophobic probes with high antimicrobial effect and moderate hemolytic activity.

Supramolecular Tools to Improve Wound Healing and Antioxidant Properties of Abietic Acid: Biocompatible Microemulsions and Emulgels.

Abietic acid, a naturally occurring fir resin compound, that exhibits anti-inflammatory and wound-healing properties, was formulated into biocompatible emulgels based on stable microemulsions with the addition of a carbamate-containing surfactant and Carbopol® 940 gel. Various microemulsion and emulgel formulations were tested for antioxidant and wound-healing properties. The chemiluminescence method has shown that all compositions containing abietic acid have a high antioxidant activity. Using Strat-M® skin-modelling membrane, it was found out that emulgels significantly prolong the release of abietic acid. On Wistar rats, it was shown that microemulsions and emulgels containing 0.5% wt. of abietic acid promote the rapid healing of an incised wound and twofold tissue reinforcement compared to the untreated group, as documented by tensiometric wound suture-rupture assay. The high healing-efficiency is associated with a combination of antibacterial activity of the formulation components and the anti-inflammatory action of abietic acid.

Microemulsions and nanoemulsions modified with cationic surfactants for improving the solubility and therapeutic efficacy of loaded drug indomethacin.

In this work, a noncovalent strategy was successfully used to modify colloidal stability andin vitroandin vivoefficacy of two amphiphilic formulations of the anti-inflammatory drug indomethacin. Namely, nanoemulsions and microemulsions based on oleic acid and nonionic surfactants have been produced and compared. The influence of cationic surfactants cetyltrimethylammonium bromide and its carbamate bearing analogue on the size characteristics, stability and ability to provide prolonged action of loaded drug indomethacin has been evaluated. Adding the positively charged molecules in the surface layer of nanoemulsions and microemulsions has shown the stability increase along with maintaining the size characteristics and homogeneity in time. Moreover, the carbamate modified analogue demonstrated beneficial behavior. Indomethacin loaded in microemulsions and nanoemulsions showed prolonged-release (10%-15% release for 5 h) compared to a free drug (complete release for 5 h). The rate of release of indomethacin from nanoemulsions was slightly higher than from microemulsions and insignificantly decreased with an increase in the concentration of the cationic surfactant. For carbamate surfactant nanocarrier loaded with fluorescence probe Nile Red, the ability to penetrate into the cell was supported by flow cytometry study and visualized by fluorescence microscopy.In vitrotests on anti-inflammatory activity of the systems demonstrated that the blood cell membrane stabilization increased in the case of modified microemulsion. The anti-inflammatory activity of the encapsulated drug was tested in rats using a carrageenan-induced edema model. Nanoemulsions without cationic surfactants appeared more efficient compared to microemulsions. Indomethacin emulsion formulations with carbamate surfactant added showed slower carrageenan-induced edema progression compared to unmodified compositions. Meanwhile, the edema completely disappeared upon treatment with emulsion loaded indomethacin after 4 h in the case of microemulsions versus 5 h in the case of nanoemulsions.

Antimicrobial Properties and Cytotoxic Effect of Imidazolium Geminis with Tunable Hydrophobicity.

Antimicrobial, membranotropic and cytotoxic properties of dicationic imidazolium surfactants of n-s-n (Im) series with variable length of alkyl group (n = 8, 10, 12, 14, 16) and spacer fragment (s = 2, 3, 4) were explored and compared with monocationic analogues. Their activity against a representative range of Gram-positive and Gram-negative bacteria, and also fungi, is characterized. The relationship between the biological activity and the structural features of these compounds is revealed, with the hydrophobicity emphasized as a key factor. Among dicationic surfactants, decyl derivatives showed highest antimicrobial effect, while for monocationic analogues, the maximum activity is observed in the case of tetradecyl tail. The leading compounds are 2-4 times higher in activity compared to reference antibiotics and prove effective against resistant strains. It has been shown that the antimicrobial effect is not associated with the destruction of the cell membrane, but is due to specific interactions of surfactants and cell components. Importantly, they show strong selectivity for microorganism cells while being of low harm to healthy human cells, with a SI ranging from 30 to 100.

The structure - Activity correlation in the family of dicationic imidazolium surfactants: Antimicrobial properties and cytotoxic effect.

BACKGROUND: The development of new effective microbicide surfactants and the search for the structure-biological activity relationship is an important and promising problem. Surfactants containing imidazolium fragment attract attention of researchers in the field of chemotherapy, because these compounds often exhibit high antimicrobial activity. The aim of this work is to identify the newly synthesized surfactants from the viewpoint of their potential usefulness in pharmacology and medicine. For this purpose, a detailed study of antimicrobial, hemolytic and cytotoxic activity of dicationic alkylimidazolium surfactants of the m-s-m (Im) series with a variable length of a hydrocarbon tail (m = 10, 12) and a spacer fragment (s = 2, 3, 4) was carried out. METHODS: Aggregation of surfactants in solutions was estimated by tensiometry and conductivity. Antimicrobial activity was determined by the serial dilution technique. Cytotoxic effects of the test compounds on human cancer and normal cells were estimated by means of the multifunctional Cytell Cell Imaging system. Cell Apoptosis Analysis was made by flow cytometry. RESULTS: The test compounds show high antimicrobial activity against a wide range of test microorganisms and do not possess high hemolytic activity. Importantly, some of them display a bactericidal activity comparable to ciprofloxacin fluoroquinolone antibiotic against Gram-positive bacteria, including methicillin-resistant strains of S. aureus (MRSA). The cytotoxicity of the compounds against normal and tumor human cell lines has been tested as well, with cytotoxic effect and selectivity strongly controlled by structural factor and kind of cell line. Superior results were revealed for compound 10-4-10 (Im) in the case of HuTu 80 cell line (duodenal adenocarcinoma), for which IC50 value at the level of doxorubicin and a markedly higher selectivity index (SI 7.5) were demonstrated. Flow cytometry assay shows apoptosis-inducing effect of this compound on HuTu 80 cells, through significant changes in the potential of mitochondrial membrane. MAJOR CONCLUSIONS: Antibacterial properties are shown to be controlled by alkyl chain length, with the highest activity demonstrated by surfactants with decyl tail, with the length of the spacer fragment showing practically no effect. The results indicate that the mechanism of cytotoxic effect of the compounds can be associated with the induction of apoptosis via the mitochondrial pathway. GENERAL SIGNIFICANCE: Selectivity against pathogenic microorganisms and low toxicity against eukaryotic cells allow considering dicationic imidazolium surfactants as new effective antimicrobial agents. At the same time, high selectivity against some cancer cell lines indicates the prospect of their using as components of new anticancer drugs.

Multi-targeted approach by 2-benzimidazolylquinoxalines-loaded cationic arginine liposomes against сervical cancer cells in vitro.

Multi-targeted approaches for inhibition of сervical cancer cells in vitro were developed by implementing two different strategies and drug combination for creation of new therapeutic target agents and for nanotechnological-enhancement of intracellular delivery. New 2-benzimidazolylquinoxalines derivatives were synthesized and characterized by combining two different pharmacophores - benzimidazole and quinoxaline rings directly bonded in their structures. Spectrophotometric technique for determination of content of compounds in various media was developed to evaluate their solubility in water and micellar solutions of surfactants. The bioavailability of poorly water-soluble 2-benzimidazolylquinoxalines was improved by PEGylated liposomes as antitumor drug delivery carriers. 2-benzimidazolylquinoxalines-loaded PEGylated liposomes, with size close to 100 nm and negative zeta potential ranging from -13 mV to -27 mV, were time-stable at room temperature. The design of liposomal formulations for improving cellular uptake and in vitro antitumor efficacy was performed by modification of liposome surface with the new arginine surfactant. The cell viability of 2-benzimidazolylquinoxalines-loaded arginine liposomes on human cancer M-Hela cells was 16% at the concentration 0.15 mg/ml. Moreover, these liposomes showed a lower toxicity (40%) against normal human Gang liver cells both at the lowest and highest tested concentrations.

Design of supramolecular biomimetic catalysts of high substrate specificity by noncovalent self-assembly of calix[4]arenes with amphiphilic and polymeric amines.

Supramolecular biomimetic catalysts of high substrate specificity are developed based on amphiphilic oxyethylated calix[4]arene bearing iso-nonyl fragments at the upper rim and hexadeca(ethylene glycol) fragments at lower rim (9CO16), and amines of amphiphilic or polymeric nature. Two critical concentrations determined by tensiometry and dye solubilization methods are probably reflect the onset of association process and transition from bimodal to monomodal size distribution revealed by the dynamic light scattering method. Amine components used may form aggregates as well, which is mediated by hydrophobic effect due to occurrence of long-chain alkyl tails. The micellar rate effect of the designed systems toward the cleavage of carboxylic acid ester is shown to be contributed by the formation of mixed aggregates with the reactive functional groups, as well as by the pKa shift of the amine and the character of the distribution of reagents in functional micelles. In the case of long-chain primary amines, an inversion of micellar rate effect (catalysis to inhibition) occurs upon transferring from the less hydrophobic substrate, p-nitrophenyl acetate, to the more hydrophobic analogs, p-nitrophenyl laurate and p-nitrophenyl caprinate. The opposite effect (inhibition of the reaction of p-nitrophenyl acetate and the acceleration of the process of hydrophobic analogs) was observed in systems based on polyethyleneimine.