Antimicrobial Activity Research Articles

In vitro antimicrobial and antioxidant activities of bioactive compounds extracted from Streptomyces africanus strain E2 isolated from Moroccan soil

This study aimed to isolate Streptomyces sp. from Moroccan terrestrial ecosystems and identify bioactive compounds through GC–MS analysis. Antimicrobial activity was assessed against various pathogenic microorganisms including Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922 and Candida albicans ATCC 60193, and multi-drug resistant strains comprising Listeria monocytogenes, Klebsiella pneumoniae 19K 929, Proteus sp. 19K1313, Klebsiella pneumoniae 20B1572, Proteus vulgaris 16C1737, and Klebsiella pneumoniae 20B1572. Based on the results of the gene sequencing of gene 16S rRNA and phylogenetic analysis, the E2 isolate belongs to the genus Streptomyces with the highest degree of resemblance (97.51%) to the Streptomyces africanus strain NBRC 101005 (NR_112600.1). The isolate exhibited broad-spectrum antibacterial activity, with maximum efficacy against Klebsiella pneumoniae 20B1572 indicated by an inhibition zone diameter of 22.5 ± 0.71mm and a minimum inhibitory concentration (MIC) of 0.0625 mg/mL. The in vitro antioxidant potential of E2 strain was determined through screening of its ethyl acetate extract against sets of antioxidant assays. The results were indicative of E2 strain displaying strong antioxidant activity against ABTS, DPPH free radicals, and FRAP. Furthermore, there was a high significant correlation (p < 0.0001) between the total phenolic and flavonoid content and antioxidant activities. The GC–MS analysis of the extract identified six volatile compounds, with Eugenol (96%) and Maltol (93%) being the most prominent. Additionally, the HPLC–UV/vis analysis revealed six phenolic compounds: gallic acid, chlorogenic acid, vanillic acid, trans-ferulic acid, ellagic acid, and cinnamic acid. Overall, the study highlights Streptomyces sp. strain E2 as a potential source of potent antimicrobial and antioxidant metabolites, offering promise in addressing antibiotic resistance and oxidative stress-related conditions.

Mechanistic characterization of fast dissolving PVP-I powder with multipolymer approaches and investigation on their molecular interaction

Povidone-iodine (PVP-I) is widely used as an antiseptic in medical applications. However, its effectiveness is limited by certain drawbacks, such as low solubility in water and high volatility. Therefore, a formulation of a stable solid PVP-I is desirable. In this study, complexes of molecular PVP-I with polyethylene glycol-polyvinyl alcohol copolymer (PEG-PVA copolymer) were considered water-soluble iodophors. Two different methods were used to prepare the solids: physical mixtures and kneading. The physical characteristics of the obtained solids were evaluated using several spectroscopic methods. The presence of iodine was confirmed by a potentiometric titration and antimicrobial activity was tested. The results showed that the PEG-PVA copolymer interacted with povidone primarily through hydrogen bonding between the hydroxyl part of the PEG-PVA copolymer and the amide part of povidone with an estimated binding energy of 3.2 kcal/mol. The amide groups polarity in povidone made them more likely to form hydrogen bonds with the PEG-PVA copolymer. Also, the protonated pyrrolidone bonded to the triiodide anions by intermolecular hydrogen bonds, which increased PVP-I solubility in water. The kneading method provided a faster dissolution rate than physical mixing and pure PVP-I. The iodine contents were within an acceptable range (10-12%), and the antimicrobial activity proved effective against Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus mutans.

Zinc Oxide-Enhanced Copper Sulfide Nanozymes Promote the Healing of Infected Wounds by Activating Immune and Inflammatory Responses.

Bacterial infection and an excessive inflammatory response are two major factors that affect the healing of infected wounds. The zinc oxide/copper sulfide (ZnO-CuS) microspheres (MSs) developed in this work can kill bacteria and resist inflammation. ZnO-CuS exhibits different enzyme-like activities depending on pH. In acidic environments, ZnO-CuS exhibits peroxidase-like (POD-like) activity and can convert hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) for sterilization. Under neutral conditions, ZnO-CuS removes reactive oxygen species (ROS) and can convert excess ROS into water and oxygen. The in vitro results of the antibacterial test demonstrate the pronounced disruption effect of ZnO-CuS on the bacterial biofilm and cell membrane. The transcriptome sequencing results of wounded animal tissue reveal that ZnO-CuS MSs increase the expression of proteins produced by immune cells, and reduce the expression levels of inflammatory factors at the wound site. Therefore, antimicrobial activity and rapid wound healing can be achieved by regulating the immune response and reducing the inflammatory response. The results from hemolysis, routine blood and blood biochemistry analyses demonstrate the excellent biosecurity of the ZnO-CuS MSs.

Chemical Composition, Biological Activity, and Application of Rosa damascena Essential Oil as an Antimicrobial Agent in Minimally Processed Eggplant Inoculated with Salmonella enterica

Rosa damascena is mostly grown for its usage in the food, medical, and perfume industries, while it is also used as an attractive plant in parks, gardens, and homes. The use of R. damascena essential oil may yield new results in relation to the antimicrobial activity of essential oils and their use mainly in extending the shelf life of foods. This study investigates the chemical composition and antimicrobial properties of Rosa damascena essential oil (RDEO) using gas chromatography–mass spectrometry (GC-MS) and various bioassays to explore its potential applications in food preservation and microorganism growth control. The GC-MS analysis revealed that RDEO is predominantly composed of phenylethyl alcohol (70%), which is known for its antimicrobial and aromatic properties. Additionally, other significant constituents were identified, including nerol, citronellol, and geraniol, which may contribute to the EOs overall bioactivity. The antimicrobial activity was assessed through the minimal inhibition concentration against five Candida yeast strains, four Gram-positive, and four Gram-negative bacteria, including biofilm-forming Salmonella enterica. Determination of minimum inhibitory concentrations (MIC) revealed the strongest effects of RDEO’s on Gram-negative species, with MIC50 values as low as 0.250 mg/mL for S. enterica. Moreover, an in situ assessment utilizing fruit and vegetable models demonstrated that the vapor phase of RDEO significantly suppressed microbial growth, with the most substantial reductions observed on kiwi and banana models. As a result of our study, the antimicrobial effect of RDEO on the microbiota of sous vide processed eggplant was detected, as well as an inhibitory effect on S. enterica during storage. The insecticidal activity against Megabruchidius dorsalis Fahreus, 1839, was also studied in this work and the best insecticidal activity was found at the highest concentrations. These results suggest that RDEO has the potential to serve as a natural antimicrobial agent in food preservation and safety applications, providing an alternative to synthetic preservatives.

Three New Spirostan Glycosides from Dracaena Cochinchinensis with NO Production Inhibitory and Antimicrobial Activity.

Three new spirostan glycosides, dracochinosides A-C (1-3), and four known steroidal glycosides (4-7) were isolated from the aerial parts of Dracaena cochinchinensis (Lour.) S.C.Chen. Their chemical structures were determined by the IR, HR-ESI-MS, 1D-, and 2D-NMR spectra. Compounds 1-3, 6 and 7 inhibited nitric oxide production in LPS activated RAW 264.7 cells with IC50 values ranging from 57.5 to 92.8 μM. In addition, all the isolated compounds exhibited at least one of seven tested microbial strains with the MIC values ranging from 0.016 to 0.128 mg/mL. This is the first report of compounds 5-7 from the genus Dracaena.

GC–MS analysis, HPLC–UV analysis, antimicrobial and antioxidant activities of extracts of wild-growing anabasis salsa native to kazakhstan desert iands

GC–MS analysis, HPLC–UV analysis, antimicrobial and antioxidant activities of extracts of wild-growing anabasis salsa native to kazakhstan desert iands

In vitro, in vivo and in silico anticancer activity and toxicity of Usnic acid extracted from the mycobiont culture of Usneabaileyi.

Lichen has widespread uses in indigenous medicinal traditions, and it has been used to treat various conditions. Among the various active compounds in the lichen, Usnic acid has unique biological activities. However, the toxicology and the mechanism of action of Usnic acid need to be examined in detail to the extent of clinical trials. Hence, the present research is aimed to isolate usnic acid from the mycobiont culture of Usnea baileyi lichen and explore its toxicological properties and those of pharmacological importance. The methanolic extract of these mycobiont cultures has shown the presence of Usnic acid via column chromatography. The Usnic acid was computationally evaluated using molecular docking studies (GLIDE docking) and MMGBSA energy calculations. The results obtained from TLC, LC-MS, UV-VIS spectrophotometer, NMR spectroscopy (1H and 13c), and FT-IR indicated the presence of Usnic acid. An acute toxicity analysis by an in vivo study using a zebrafish animal model showed acute toxicity. The standard disc diffusion and DPPH assay suggested an antimicrobial and antioxidant activity with this lichen compound. The in vitro analysis of Usnic acid in G361 skin cancer cell lines demonstrated its anticancer potential against malignant melanoma. Furthermore, a molecular in silico study returned a good docking score of -7.977, and the MMGBSA free energy was measured as -18 and -30. Therefore, further extensive research on Usnic acid might lead to the development of novel anticancer drugs from the natural sources.

Dual role of ramR mutation in enhancing immune activation and elevating eravacycline resistance in Klebsiella pneumoniae

AbstractThe rise of Klebsiella pneumoniae resistant to last‐resort antimicrobials poses an urgent threat to global health. The ramR‐ramA regulatory system critically influences drug resistance by regulating the AcrAB‐TolC efflux pump, which also plays a crucial role in the pathogenicity of K. pneumoniae. However, the mechanism of the ramR‐ramA system on bacteria‐host interaction remains unclear. To determine how specific mutations in ramR influence eravacycline (ERV) resistance and their impact on the immune activation capabilities of K. pneumoniae, thereby highlighting potential targets for therapeutic intervention, we performed genetic sequencing to identify mutations in ramR. Then, the CRISPR‐Cas9 technology was employed to construct specific ramR mutations into K. pneumoniae, which were then subjected to phenotypic and functional assays in both in vitro and in vivo (mouse models, macrophage, and blood‐killing experiment) settings. ramR L58P and F165L genetic alterations disrupt the binding affinity of RamR to the ramA promoter, thereby upregulating the efflux pump expression and increasing ERV minimum inhibitory concentration values up to 64‐fold compared to the wild‐type. Concurrently, these mutations modulate lipid A structure by increasing 2‐hydroxy fatty acid chain abundance. In mouse models, ramR L58P and F165L mutants showed lower bacterial burden in organs (spleen, lung, and kidney) 6 h post‐infection, and are fast cleared in 48 h. Furthermore, despite lower intracellular bacterial loads, ramR L58P and F165L mutants induce heightened pro‐inflammatory cytokine responses in macrophages and elevate systemic cytokine levels (interleukin [IL]2, IL4, IL6, IL12, interferon‐α, and interferon‐γ) in human blood co‐culture experiments. This study illuminates the critical role of ramR mutations in conferring ERV resistance and enhancing immune responses in K. pneumoniae. The dual impact of these mutations on both antimicrobial resistance and immune activation not only underscores the challenges in treating infections but also advocates for heightened surveillance and innovative strategies to counteract the emerging threat of antimicrobial‐resistant K. pneumoniae.

Quality Characteristics and Essential Oil Properties of Thymus capitatus, Mentha piperita, and Sideritis cypria Dried under Different Conditions

The drying of medicinal and aromatic plants (MAPs) is one of the main preservation methods for these products that can prolong their shelf life, if performed properly. The current study aimed to examine the effects of different drying conditions (sun, shade, and oven drying at 42 °C) on the quality characteristics of Thymus capitatus, Mentha piperita, and Sideritis cypria; their essential oil (EO) yield; and their biological properties (antioxidant and antibacterial activities). According to the results of the current study, oven drying resulted in faster moisture loss for all investigated species and slightly darker products. For T. capitatus, sun drying resulted in higher EO carvacrol content, whereas EOs obtained from shade and oven drying (at 42 °C) presented high total phenolic content and great antimicrobial activity. For M. piperita, shade drying resulted in a higher EO yield and higher iso-menthone content, whilst the EO obtained from oven-dried mint plants presented great antibacterial activity against the investigated foodborne pathogens. S. cypria plants dried in an air-ventilated oven produced an EO rich in β-caryophyllene and α-pinene, which also presented great antioxidant and antibacterial activity. The findings of the current study indicate that traditional drying methods, such as sun and shade, can result in good-quality dried MAPs that can yield EOs with significant biological activities, along with minimum energy consumption and lower carbon dioxide production (lower environmental carbon footprint), as opposed to oven drying. However, the drying-process duration could be a limitation at the industrial scale.

Poly(lactic acid) and copper‐modified montmorillonite nanocomposite films for antimicrobial food packaging

AbstractPolymer‐based nanocomposites loaded with metal nanoparticles are an interesting alternative for the development of antimicrobial food packaging. However, affinity and dispersion of metal nanoparticles could be improved using nanoclays. Therefore, nanocomposite films based on poly(lactic acid) (PLA) and copper modified‐montmorillonite were developed by melt‐extrusion technique. Copper‐modified montmorillonite at different valence states (MtCu2+ and MtCu0) were prepared. The nanocomposites were evaluated by means of their structural, optical, thermal and antimicrobial properties. Results showed that both nanoclays were intercalated in PLA but MtCu2+ was better dispersed. Therefore, color change ΔE &lt; 2, higher thermal stability and higher elongation at break was evidenced for MtCu2+/PLA in comparison to pure PLA. Contrary, MtCu0 showed the displacement of Cu0 nanoparticles to the polymer matrix. These free nanoparticles were agglomerated and they leaded on a ΔE &gt; 9 for MtCu0/PLA nanocomposites compared with PLA. Moreover, Cu0 nanoparticles in the matrix accelerated the thermal degradation and decreased the ductility of nanocomposites. On the other hand, both nanocomposites were able to reduce over 2 log10 of Escherichia coli growth and MtCu2+/PLA showed a higher antimicrobial activity against Listeria innocua. These results showed the potential of nanocomposite films based on PLA and copper‐modified montmorillonite for antimicrobial food packaging applications.

Activated Charcoal-Alginate Platform for Simultaneous Local Delivery of Bioactive Agents: At the Nexus of Antimicrobial and Cytotoxic Activity of Zn2+ Ions

Antimicrobial resistance (AMR) is a global public health threat that affects cancer patients more than the general population. In this work, a composite system based on Zn-alginate hydrogel and activated charcoal (AC) particles that, upon contact with physiological fluids, simultaneously releases bioactive agents (Zn2+ and AC particles impregnated with povidone–iodine) was designed to locally address specific problems characteristic for malignant wounds (MWs). This composite was comprehensively investigated in vitro regarding its morphology (field-emission scanning electron microscopy), Zn2+ release (flame atomic absorption spectrometry), iodine adsorption and desorption from AC particles (energy dispersive X-ray analysis and UV–visible spectroscopy) as well as its antimicrobial and antitumor activity. With respect to the ongoing AMR crises, antimicrobial activity was tested against a wide range of wild multi-drug resistant bacterial and yeast strains, all isolated from patient wounds. Since Zn2+ ions proved to be selectors of resistant strains of bacteria, the synergistic activity of AC particles and adsorbed iodine was shown to be crucial for excellent antibacterial activity. On the other hand, the synergy of AC particles and Zn2+ ions showed an equally strong antifungal effect. In addition, antimicrobial concentrations of Zn2+ ions showed cytotoxic activity against two cancer cell lines derived from cancers affecting skin either as metastatic cancer (breast cancer MDA-MB-453 cell line) or primary cancer of the skin (malignant melanoma Fem-X cell line), which enables Zn2+ ions to be further investigated as potent local agents targeting malignant cells.

Fabrication of Multifunctional Green-Synthesized Copper Oxide Nanoparticles Using Rumex vesicarius L. Leaves for Enhanced Photocatalytic and Biomedical Applications

Recently, the use of plant extracts has emerged as an innovative approach for the production of various nanoparticles. Enhancing green methods for synthesizing copper oxide (CuO) nanoparticles (NPs) is a key focus in the field of nanotechnology. This study presents a novel and eco-friendly synthesis of CuO NPs using Rumex vesicarius L. leaf extracts, offering a cost-effective and efficient method. The synthesized CuO NPs were evaluated for their cytotoxic effects against human cervical carcinoma (HeLa) cells, as well as their photocatalytic and antimicrobial activities. The morphology, size, and structural properties of the CuO NPs were characterized using various analytical techniques. X-ray diffraction (XRD) analysis confirmed the pure crystalline structure of the CuO NPs with a size of 19 nm, while transmission electron microscopy (TEM) showed particle sizes ranging from 5 to 200 nm. The photocatalytic performance of the CuO NPs was assessed through the photodegradation of crystal violet (CV) and methylene blue (MB) dyes under UV light. The NPs exhibited excellent decolorization efficiency, effectively degrading dyes in aqueous solutions under irradiation. Furthermore, the green-synthesized CuO NPs displayed strong antibacterial and antifungal activities against a variety of human pathogens. They also demonstrated significant dose-dependent cytotoxicity against the HeLa cancer cell line, with an IC50 value of 8 ± 0.54 μg/mL.

Role of Peptide Associations in Enhancing the Antimicrobial Activity of Adepantins: Comparative Molecular Dynamics Simulations and Design Assessments

Adepantins are peptides designed to optimize antimicrobial biological activity through the choice of specific amino acid residues, resulting in helical and amphipathic structures. This paper focuses on revealing the atomistic details of the mechanism of action of Adepantins and aligning design concepts with peptide behavior through simulation results. Notably, Adepantin-1a exhibits a broad spectrum of activity against both Gram-positive and Gram-negative bacteria, while Adepantin-1 has a narrow spectrum of activity against Gram-negative bacteria. The simulation results showed that one of the main differences is the extent of aggregation. Both peptides exhibit a strong tendency to cluster due to the amphipathicity embedded during design process. However, the more potent Adepantin-1a forms smaller aggregates than Adepantin-1, confirming the idea that the optimal aggregations, not the strongest aggregations, favor activity. Additionally, we show that incorporation of the cell penetration region affects the mechanisms of action of Adepantin-1a and promotes stronger binding to anionic and neutral membranes.

Synthesis, Crystallization, Antimicrobial Activity, and Molecular Docking of Crystal bis(6-methoxy-7-methylpurine)-bis(μ-chloro) copper(II) Complex

Synthesis, Crystallization, Antimicrobial Activity, and Molecular Docking of Crystal bis(6-methoxy-7-methylpurine)-bis(μ-chloro) copper(II) Complex

ENGINEERED CHITOSAN NANOPARTICLES FOR ENCAPSULATION OF THYMOL

This study successfully obtained chitosan thymol nanoparticles using an electrohydrodynamic technique, which is a simple one-step procedure. The morphological and physical characterization, antioxidant, and antimicrobial activity assessments of electrosprayed thymol-loaded chitosan nanoparticles (CTNPs) were carried out. The ABTS assay and the agar well diffusion test were used to determine the antioxidant and antimicrobial activities of the CTNP samples, respectively. The results showed that CTNPs possessed efficient antimicrobial capacity against B. cereus, S. aureus, E. coli, and S. typhimurium. CTNPs indicated a radical scavenging activity of 90% regarding the ABTS assay. CTNPs with biological activities could be an effective alternative for practical food safety and health applications. In this study, the use of electrohydrodynamic atomization technique to produce biopolymer nanoparticles present a novel approach for encapsulating thymol-like volatile active agents.

Impact of Pluronic F-127 on the Stability of Quercetin-Loaded Liposomes: Insights from DSC Preformulation Studies

The aim of the present study is to evaluate the stability of DMPC:Pluronic F-127 and DPPC:Pluronic F-127 liposomes, both with and without incorporated quercetin. Quercetin belongs to the class of flavonoids and has shown antioxidant, antiviral, anti-inflammatory, anti-cancer, and antimicrobial activities. Dynamic light scattering, electrophoretic light scattering, and differential scanning calorimetry (DSC) were utilized to investigate the cooperative behavior between liposomal components and its effect on stability. All formulations were stored at 4 °C and 25 °C and studied over 42 days. Furthermore, the interaction of the final formulations with serum proteins was assessed to evaluate the potential of Pluronic F-127 as a stabilizer in these liposomal nanosystems. This study highlights the impact of DSC in preformulation evaluations by correlating thermal behavior with quercetin incorporation and variations in size and the polydispersity index. According to the results, quercetin increased the fluidity and stability of liposomal nanosystems, while Pluronic F-127 was not sufficient for effective steric stabilization. Additionally, DSC thermograms revealed the integration of Pluronic F-127 into lipid membranes and showed phase separation in the DMPC nanosystem. In conclusion, the results indicate that the DPPC:Pluronic F-127:quercetin nanosystem exhibited the desired physicochemical and thermotropic properties for the effective delivery of quercetin for pharmaceutical purposes.

Antimicrobial, Antifungal, and Insecticidal Activities of Scolymus Grandiflorus Essential Oil Rich in Davanoid Compounds

Background: This study explores the antimicrobial, antifungal, and insecticidal properties of Scolymus grandiflorus essential oil, examining its potential uses in the fields of pharmacology and agriculture. Materials and Methods: The essential oil obtained by hydrodistillation was studied by GC and GC/MS. The antibacterial capacity of the essential oil was determined against two Gram-positive and three Gram-negative bacterial species. The antifungal activity of the essential oil was investigated against two fungi responsible for many fruit and vegetable diseases. The insecticidal activity of essential oil was evaluated against larvae, pupae, and adult flies of Ceratitis capitata. Results: The GC and GC-MS analysis of the essential oil of the roots of S. grandiflorus revealed the predominant presence of davanoids, representing more than 80% of its chemical composition. The results of the disc diffusion test showed significant antimicrobial activity. The essential oil inhibited the growth of Salmonella typhi (25 mm), Staphylocoque aureus (18 mm), and Escherichia coli (17 mm), with inhibition diameters comparable to those of gentamicin. The essential oil significantly inhibited mycelial growth, with up to 98% inhibition for Fusarium solani and 73% for Alternaria alternata at 8 μL/mL. Insecticidal activity was most pronounced on adult flies, followed by pupae and finally larvae. Conclusion: Tests on the essential oils of S. grandiflorus revealed promising characteristics as insecticidal, antifungal, and antimicrobial agents. These results could be used in the development of new solutions to control pathogens responsible for plant diseases and mycotoxin-producing organisms.

Computer prediction of toxicity of new S-alkyl derivatives of 1,2,4-triazole

1,2,4-Triazole derivatives are of researchers’ significant interest due to their diverse biological properties, such as antimicrobial, anti-inflammatory, anticancer, and antioxidant activities. The integration of a 2-bromo-4-fluorophenyl fragment into the triazole structure can significantly enhance these activities. However, the evaluation of the toxicity of such compounds remains a critically important aspect for their practical application. To reduce the time and cost of experimental studies, QSAR (Quantitative Structure-Activity Relationship) methods are actively used, allowing the prediction of toxicity based on the molecular structure of compounds. Aim of the study. To assess the toxicity of new S-derivatives of 5-(2-bromo-4-fluorophenyl)-4-R-1,2,4-triazol-3-thiols using the QSAR method, specifically to predict acute toxicity parameters (LD50), and to determine the influence of different (length) radicals on the toxicity of these compounds. Materials and methods. The objects of the virtual study were derivatives of 5-(2-bromo-4-fluorophenyl)-4-ethyl-1,2,4-triazol-3-thiols. They were evaluated at the Department of Toxicological and Inorganic Chemistry of the Zaporizhzhia State Medical and Pharmaceutical University. The toxicity assessment was conducted using the nearest neighbor method via the Toxicity Estimation Software Tool (TEST). The prediction of the lethal dose (LD50) for rats was based on the structural similarity of the studied compounds with known substances, for which experimental toxicity data are available. Results. The conducted QSAR analysis demonstrated that structural changes in S-derivatives of 5-(2-bromo-4-fluorophenyl)-4-ethyl-1,2,4-triazol-3-thiols significantly affect the predicted toxicity. The primary factor influencing the changes in LD50 values is the variation of radicals at the 5th position of the triazole ring. Conclusions. The results of the study showed, that the toxicity of new S-alkyl derivatives of triazol-3-thiols depends on the type of alkyl substituent. Compounds with propyl to heptyl fragments exhibit increased toxicity, while derivatives with thiol, octyl, nonyl, and decyl residues are characterized by lower toxicity.

QSAR prediction of toxicity for a new 1,2,4-triazole derivatives with 2-bromo-5-methoxyphenyl fragment

New derivatives of 1,2,4-triazole are promising research targets due to their unique biological properties, including antimicrobial, antifungal, antitumor, and antioxidant activities. The introduction of the 2-bromo-5-methoxyphenyl fragment into the triazole structure potentially enhances these properties. However, the issue of toxicity for such compounds remains a critical factor for their further application. To reduce experimental costs and time, QSAR (Quantitative Structure-Activity Relationship) methods are widely applied, allowing to predict compounds toxicity based on their molecular structure. The aim of this study was to evaluate the toxicity of new derivatives of 5-(2-bromo-5-methoxyphenyl)-4-R-1,2,4-triazole-3-thiols, their acids, and esters using the QSAR method to predict parameters of acute toxicity (LD50) and to assess the influence of various radicals on the toxicity of the compounds. Materials and methods. The objects of this study were derivatives of 5-(2-bromo-5-methoxyphenyl)-4-R-1,2,4-triazole-3-thiols, synthesized at the Department of Toxicological and Inorganic Chemistry of Zaporizhzhia State Medical and Pharmaceutical University. The nearest neighbor method was used for toxicity evaluation, applying the Toxicity Estimation Software Tool (TEST). The prediction of rats lethal dose (LD50) was based on the structural similarity of the studied compounds with known substances that have experimental toxicity data. Results. The QSAR analysis revealed that structural modifications in the derivatives of 5-(2-bromo-5-methoxyphenyl)-4-R-1,2,4-triazole-3-thiols significantly influence their toxicity. Specifically, increasing the size of the radicals, especially through the introduction of aromatic fragments, contributed to the enhanced safety of the compounds, as evidenced by the increase in LD50 values. The highest LD50 values were observed for compounds containing phenyl radicals. Conclusions. The results of this study indicate the feasibility of using QSAR models to predict the toxicity of 1,2,4-triazole derivatives containing a 2-bromo-5-methoxyphenyl fragment. The observed trend of increasing safety with the introduction of larger aromatic radicals can be used for the rational design of new compounds with improved toxicological properties.

Antimicrobial Macrocycles - Synthesis, Characterization, and Activity Comparison with Their Linear Polycationic Analogues.

One of the promising candidates for new antimicrobial agents is membrane-lytic compounds that kill microbes through cell membrane permeabilization, such as antimicrobial peptides (AMPs) and their synthetic mimics (SMAMPs). Although SMAMPs have been under investigation for nearly 30 years, a few challenges must be addressed before they can reach clinical use. In this work, a step-growth polymerization leading to already-known highly antimicrobial ionenes was redirected toward the formation of macrocyclic quaternary ammonium salts (MQAs) employing a high dilution principle. Antimicrobial assays and cytotoxicity studies revealed the high antimicrobial activity of MQAs and better selectivity than their polymeric analogues. Therefore, MQAs seem to be a new class of promising antibacterial agents. Additionally, membrane-lytic experiments using large unilamellar liposomes (LUVs) and whole cells revealed significant differences between MQAs and ionenes in their ability to adsorb onto the surface of LUVs and microbes as well as their ability to permeate the lipid bilayer.