Search Results (353)

Persistent bacteria (PB) are a subpopulation of dormant cells that tolerate high antibiotic concentrations and cause chronic, hard-to-treat infections, posing a serious global health threat. In this study, the antibacterial efficacy of six cationic polymers, poly(hexamethylene guanidine) (PHMG), polyethyleneimines of different molecular weights, α-polylysine, ε-polylysine, and polyacrylamide, against persistent bacteria was systematically evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of these cationic polymers against susceptible and persistent methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and Escherichia coli (E. coli) were determined using a microbroth dilution method, while cytotoxicity to mouse fibroblast (L929) cells was assessed via MTT assay. PHMG demonstrated superior antibacterial activity, with MBC values as low as 2 μg/mL against persistent MSSA, markedly outperforming the other polymers tested. The key novelties of this work are (i) the first establishment of a cationic polymer library with diverse structural parameters for persistent bacteria clearance, offering a potential strategy for treating recalcitrant infections; and (ii) the elucidation of quantitative correlations between polymer charge density and hydrophobic chain segments with antimicrobial efficacy through structure–activity relationship analysis, providing a theoretical basis for the rational design of anti-persistent materials. Full article

Diaza-peptidomimetics are constrained compounds that mimic the biological efficacy of peptides while offering increased stability. We have previously reported the synthesis of bis-cyclic guanidine heterocyclic peptidomimetics as opioid ligands with mixed μ-, κ- and δ-opioid receptor interactions and their potential activity as novel analgesics. Using the same approach, we report here the synthesis of sulfonated and piperazine-tethered bis-cyclic guanidines and their in vitro screening results from radioligand competition binding assays at the μ- (MOR), δ- (DOR), and κ- (KOR) opioid receptors. Full article

Zeolites are widely used as adsorbents due to their porous structure and ion-exchange capabilities. However, their adsorption efficiency for heavy metal ions remains limited. To enhance their performance, the natural zeolite heulandite (Z) was functionalized with guanidine derivatives: N-[3-(triethoxysilyl)propyl]guanidine (1), -aminoguanidine (2), and -acetyl-guanidine (3). The resulting materials (Z1–Z3) were evaluated for their ability to adsorb Co²⁺, Cu²⁺, and Ni²⁺ from aqueous solutions. The composition and structure of silanes 1–3 were confirmed by FT-IR and ¹H and ¹³C NMR spectroscopy methods. The modified zeolites were characterized using nitrogen adsorption/desorption (BET) and SEM-EDX to confirm their functionalization and assess the structural changes. A TGA-DSC was used to determine the thermal stability. The adsorption experiments were conducted in single and multi-ionic aqueous solutions at pH 5.0 to evaluate metal uptake. Functionalization significantly improved the adsorption efficiency, with Z1–Z3 showing a three to six times greater adsorption capacity than the unmodified zeolite. The adsorption efficiency followed the trend Cu²⁺ > Co²⁺ > Ni²⁺, primarily due to chelate complex formation between the metal ions and guanidine groups. The SEM-EDX confirmed the co-localization of nitrogen atoms and metal ions. The functional materials (Z1–Z3) exhibited strong potential as adsorbents for noble, heavy, and toxic metal ions, and could find applications in industry, agriculture, ecology, medicine, chemistry, wastewater treatment, soil remediation, chemisorption, filtration, chromatography, etc. Full article

A series of Zn complexes containing guanidine– and amidine–phenolate ligands were synthesized and evaluated as catalysts for the polymerization of rac-lactide at 130 °C, under solvent-free conditions, giving rate constants in the range of 0.71–4.37 × 10^–4 s^–1. Polymerization under identical conditions with the guanidine– and amidine–phenol proligands themselves used as catalysts gave values in the range of 0.30–2.45 × 10^–4 s^–1. The stereoselective production of polylactic acid from either the Zn complexes or the proligands was limited (P_r = 0.47–0.62). The molecular weight of the polymers was lower than expected for living polymerizations due to chain transfer and/or transesterification but were comparable to those obtained in control experiments with Sn(Oct)₂. Full article

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have put an end to the era of the biguanides as oral antidiabetics. The strongly hygroscopic metformin (1-1-dimethylbiguanide), first synthesized 1922 and resuscitated as an oral antidiabetic (type 2 of the elderly) compound first released in 1959 in France and in other European countries, was used in the first large multicenter prospective long-term trial in England in the UKPDS (1977–1997). It was then released in the USA after a short-term prospective trial in healthy overweight “young” type 2 diabetics (mean age 53 years) in 1995 for oral treatment of type 2 diabetes. It was, however, prescribed to mostly multimorbid older patients (above 60–65 years of age). Metformin is now the most used oral drug for type 2 diabetes worldwide. While intravenous administration of biguanides does not have any glucose-lowering effect, their oral administration leads to enormous increase in their intestinal concentration (up to 300-fold compared to that measured in the blood), to reduced absorption of glucose from the diet, to increased excretion of glucose through the stool, and to decrease in insulin serum level through increased hepatic uptake and decreased production. Intravenously injected F18-labeled glucose in metformin-treated type 2 diabetics accumulates in the small and even more in the large intestine. The densitometry picture observed in metformin-treated overweight diabetics is like that observed in patients after bowel-cleansing or chronically taking different types of laxatives, where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to “attraction” of glucose from the hepatocyte into the intestine, possibly through the insulin-mediated uptake in the hepatocyte and its secretion into the bile. Furthermore, these compounds have also a diuretic effect (loss of sodium and water in the urine) Acute gastrointestinal side effects accompanied by fluid loss often lead to the drugs’ dose reduction and strongly limit adherence to therapy. Main long-term consequences are “chronic” dehydration, deficiency of vitamin B12 and of iron, and, as observed for all the biguanides, to “chronic” increase in fasting and postprandial lactate plasma level as a laboratory marker of a clinical condition characterized by hypotension, oliguria, adynamia, and evident lactic acidosis. Metformin is not different from the other biguanides: synthalin B, buformin, and phenformin. The mechanism of action of the biguanides as antihyperglycemic substances and their side effects are comparable if not even stronger (abdominal pain, nausea, vomiting, diarrhea, fluid loss) to those of laxatives. Full article

Prion diseases such as chronic wasting disease involve the conformational conversion of the cellular prion protein (PrP^C) into its misfolded, β-rich isoform (PrP^Sc). While chemical denaturants such as guanidine hydrochloride (GdnHCl) and urea are commonly used to study this process in vitro, their distinct molecular effects on native and misfolded PrP conformers remain incompletely understood. In this study, we employed 500 ns all-atom molecular dynamics simulations and essential collective dynamics analysis to investigate the differential effects of GdnHCl and urea on a composite PrP^C/PrP^Sc system, where white-tailed deer PrP^C interfaces with a corresponding PrP^Sc conformer. GdnHCl was found to preserve interfacial alignment and enhance β-sheet retention in PrP^Sc, while urea promoted partial β-strand dissolution and interfacial destabilization. Both denaturants formed transient contacts with PrP, but urea displaced water hydrogen bonds more extensively. Remarkably, we also observed long-range dynamical coupling across the PrP^C/PrP^Sc interface and between transiently bound solutes and distal protein regions. These findings highlight distinct, denaturant-specific mechanisms of protein destabilization and suggest that localized interactions may propagate non-locally via mechanical or steric pathways. Our results provide molecular-scale insights relevant to prion conversion mechanisms and inform experimental strategies using GdnHCl and urea to modulate misfolding processes in vitro. Full article

The enormous potential of bacteriotherapy in disease treatment and prevention has created a large probiotic market. Significant challenges exist in assessing probiotic quality, efficacy and viability. Lactic acid bacteria (LAB) are commonly used probiotics and the most abundant of the vertebrate microbiota. The goal of this study was to make MRS agar specific for probiotic Ligilactobacillus animalis NP51, since the current formulation is not sufficiently selective. Here, 53 chemicals were screened to identify compound(s) that reduced the growth of non-LAB and fungi on de Mann, Rogosa, and Sharpe (MRS) agar, and which were selective for LAB and specifically the probiotic strain NP51. Cattle feed was selected as the sample type, as it is commonly amended with Lactobacillus or yeast probiotics and often includes silage, a diverse microbial consortium of fungi and LAB. Modified MRS was evaluated for its effectiveness in determining probiotic viability and the detection of L. animalis NP51 in cattle feed, amended with this probiotic. qPCR was used to specifically detect and enumerate NP51 in commercial and experimental feed samples. For four selective agents, nystatin, guanidine hydrochloride, CuSO₄, and ZnCl, it was identified that when used together, they reduced the growth of bacteria and fungi, but did not inhibit the Lactobacillus probiotic NP51 and other LAB. Metagenomic analysis revealed LAB as the major group cultivated on modified MRS agar from the plating of cattle feed amended with silage. As an enrichment, modified MRS broth improved the qPCR detection of probiotic strain NP51. This study illustrated that improvements can be made to existing bacteriological media for enumerating probiotic NP51 and determining the product’s viability. Full article

CO₂-responsive polymers have emerged as a significant class of smart materials, distinguished by their ability to reversibly alter their properties upon exposure to CO₂. Due to CO₂’s abundant availability, low cost, non-toxicity, energy efficiency, and excellent biocompatibility, these polymers offer remarkable environmental and practical advantages. This review succinctly explores recent advancements in the synthesis, mechanisms, and applications of CO₂-responsive polymers, emphasizing the pivotal roles of specific acidic and basic functional groups such as carboxylic acids, phenolic groups, amines, amidines, guanidines, and imidazoles. Advanced polymerization techniques including free radical polymerization (FRP), atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT), and nitroxide-mediated polymerization (NMP) are critically evaluated for their precision and flexibility in polymer design. Significant applications in smart separation, carbon capture, drug delivery, desalination, emulsions, tissue engineering, and sensing technologies are discussed comprehensively. Although substantial progress has been made, ongoing challenges include enhancing response speed, durability, sustainability, and economic viability. Future research is recommended to focus on innovative polymer structures, computational modeling, hybrid materials, and greener synthesis methods. This review aims to inspire continued exploration and practical utilization of CO₂-responsive polymers to address pressing environmental and technological needs. Full article

Background/Objectives: While various nucleoside and nucleotide analogs have been approved as anticancer and antiviral drugs, their limitations, including low bioavailability and chemotherapeutic resistance, encourage the development of novel structures. In this context, and motivated by our previous findings on bioactive 3′-O-substituted xylofuranosyl nucleosides and 5-guanidine xylofuranose derivatives, we present herein the synthesis and biological evaluation of 5′-guanidino furanosyl nucleosides comprising 6-chloropurine and uracil moieties and a 3-O-benzyl xylofuranosyl unit. Methods: The synthetic methodology was based on the N-glycosylation of a 5-azido 3-O-benzyl xylofuranosyl acetate donor with the silylated nucleobase and a subsequent one-pot sequential two-step protocol involving Staudinger reduction of the thus-obtained 5-azido uracil and N⁷/N⁹-linked purine nucleosides followed by guanidinylation with N,N′-bis(tert-butoxycarbonyl)-N′′-triflylguanidine. The molecules were evaluated for their anticancer and anti-neurodegenerative diseases potential. Results: 5′-Guanidino 6-chloropurine nucleosides revealed dual anticancer and butyrylcholinesterase (BChE)-inhibitory effects. Both N⁹/N⁷-linked nucleosides exhibited mixed-type and selective submicromolar/micromolar BChE inhibiton. The N⁹ regioisomer was the best inhibitor (K_i/K_i′ = 0.89 μM/2.96 μM), while showing low cytotoxicity to FL83B hepatocytes and no cytotoxicity to human neuroblastoma cells (SH-SY5Y). Moreover, the N⁹-linked nucleoside exhibited selective cytotoxicity to prostate cancer cells (DU-145; IC₅₀ = 27.63 μM), while its N⁷ regioisomer was active against all cancer cells tested [DU-145, IC₅₀ = 24.48 μM; colorectal adenocarcinoma (HCT-15, IC₅₀ = 64.07 μM); and breast adenocarcinoma (MCF-7, IC₅₀ = 43.67 μM)]. In turn, the 5′-guanidino uracil nucleoside displayed selective cytotoxicity to HCT-15 cells (IC₅₀ = 76.02 μM) and also showed neuroprotective potential in a Parkinson’s disease SH-SY5Y cells’ damage model. The active molecules exhibited IC₅₀ values close to or lower than those of standard drugs, and comparable, or not significant, neuro- and hepatotoxicity. Conclusions: These findings demonstrate the interest of combining guanidine moieties with nucleoside frameworks towards the search for new therapeutic agents. Full article

The adhesion between rubber compounds and textile cords plays a critical role in determining the overall performance and durability of rubber-based composites, particularly in tire applications. Despite extensive research on adhesion mechanisms, optimizing adhesion through systematic modeling remains challenging due to the complex interactions between rubber formulations, textile treatment, and processing conditions. This study presents an integrated experimental and predictive modeling approach to investigate and optimize the adhesion performance of nylon 6.6 textile cords in rubber compounds. Initially, the effects of different accelerator types—including diphenyl guanidine (DPG), 2,2′-Dithiobis(benzothiazole) (MBTS), N-tert-butyl-2-benzothiazole sulfenamide (TBBS), and N-cyclohexyl-2-benzothiazole sulfenamide (CBS)—on adhesion properties were systematically evaluated. Key parameters such as cure characteristics, Mooney viscosity, and mechanical properties of the rubber compounds were analyzed using a moving die rheometer (MDR), Mooney viscometer, and tensometer. To enhance adhesion performance, a statistical optimization approach based on the Box–Behnken design was employed, focusing on the influence of accelerator, curing agent, and resin contents. The results indicate that an optimized rubber formulation comprising 1.6 phr curing agent, 0.3 phr resin (HMMM), and 0.5 phr accelerator (MBTS) yields the highest adhesion strength. This study provides the first systematic modeling of adhesion between nylon 6.6 textile cords and rubber compounds using response surface methodology (RSM), offering valuable insights into the material design for improved interfacial bonding in tire manufacturing. Full article

Handling cultured isolates and clinical, environmental, or wildlife surveillance samples containing Risk Group 3 and 4 pathogens presents considerable biosafety challenges in minimizing human exposure during processing and transport. Safe handling typically requires high- or maximum-containment facilities, demanding substantial logistical planning and resources. We evaluated PrimeStore Molecular Transport Medium (PS-MTM), a guanidine-based solution created to kill pathogens and preserve nucleic acids at ambient temperatures, for inactivating Crimean-Congo hemorrhagic fever, eastern equine encephalitis, Ebola, Hendra, Japanese encephalitis, Lassa, Marburg, Nipah, Rift Valley fever, and West Nile viruses. To mimic diagnostic conditions, human whole blood spiked with any of these viruses was incubated with PS-MTM for 20-, 30-, or 60-min. Samples with titers up to 10⁷ PFU/mL exposed to PS-MTM at all time points resulted in complete loss of infectivity judged by plaque assays. A 30-min incubation provided a 50% safety margin over the minimum inactivation time and was used for quantification with the tissue culture infectious dose (TCID₅₀) assay, enabling evaluation of PS-MTM’s activity for viruses that do or do not produce well-defined plaques. Results confirmed that PS-MTM inactivated all tested viruses at titers up to 10⁷ TCID₅₀/mL, underscoring its reliability for enhancing biosafety in diagnostics, outbreak management, and surveillance. Full article

Guanidine disinfectants are cationic polymers recognized for their effective sterilization properties and their ability to prevent bacterial resistance. As a result, they are widely utilized in medical, healthcare, household, and animal husbandry settings. However, the bactericidal effects and mechanisms of guanidine in marine aquaculture systems remain unclear due to the polymeric nature of guanidine ions and the complexity of marine environments. The inhibitory effects and bactericidal mechanisms of polyhexamethylene biguanide (PHMB) on key pathogens and probiotics are examined in this study. It was shown that PHMB had inhibitory effects on Vibrio parahaemolyticus (VP), Photobacterium damselae subsp. damselae (PDD), Bacillus subtilis (BS), Escherichia coli (EPEC), and Staphylococcus aureus (SAU), with minimum inhibitory concentrations (MICs) ranging from 3.91 to 125.0 µg/mL, and minimum bactericidal concentrations (MBCs) from 15.63 to 250.0 µg/mL. A stronger bactericidal effect of PHMB on marine bacteria compared to EPEC and SAU was exhibited. It was shown in ion interference experiments that the addition of calcium ions reduced the bactericidal effectiveness of PHMB against VP and PDD by 87.73% and 53.35%, respectively. At a PHMB concentration of 62.50 µg/mL, minor changes in cell surface potential energy (CSPE) were exhibited by Gram-positive bacteria (SAU and BS), while more significant alterations were shown by Gram-negative pathogens. It was revealed by propidium iodide staining and scanning electron microscopy (SEM) analysis that the bacterial cell membrane was directly disrupted by PHMB. DNA and RNA release analysis further revealed that following PHMB treatment, changes in membrane permeability were exhibited by Gram-negative pathogens, with a significant increase in extracellular DNA content as PHMB concentration increased. No such effect was observed in Gram-positive bacteria. Additional evidence was provided by the findings that PHMB effectively inhibits bacterial pathogens in mariculture systems, with a significantly stronger inhibitory effect on Gram-negative pathogens than on Gram-positive bacteria. These results indicated that PHMB could serve as a new antimicrobial agent in mariculture. Full article

A new alkaloid (orychophragvioline A) and nine known compounds were yielded from the seeds of Orychophragmus violaceus. Their structures were determined by various spectroscopic techniques and single-crystal X-ray diffraction. Orychophragvioline A is a rare alkaloid with an unusual 1-methyl-4-phenyl-2,3-diketopiperazine skeleton connected with a guanidine group via an amide bond. The results of antitumor tests in vitro showed that it exhibited prominent cytotoxicity against Hela cells with an IC₅₀ value of 11.95 ± 1.52 μM. Further investigations suggested that it significantly inhibited cellular proliferation, migration, and invasion in a dose-dependent manner, thus inducing the apoptosis of Hela cells. These findings indicate that orychophragvioline A can be regarded as a potential natural leading compound against cervical cancer. Full article

This study describes the synthesis, interaction with DNA, and transfection efficacy of eight lipidated compounds based on a recently published non-lipidated parent molecule, an octamer of 2,3-l-Dap, carrying the guanidine group on its side chain. The compounds obtained were found to be non-toxic up to 5 µM and efficient DNA binders and showed greater transfection efficiency than the parent compound, with two leading molecules containing acetic and decanoic moieties. DLS experiments indicated two groups of interaction with DNA. One group modified by short-chain lipids (up to eight carbon atoms in the main chain) forms large structures due to the aggregation of multiple nucleic acids. The second group (from twelve to sixteen carbon atoms) with dominant condensation creates smaller forms and is less effective in transporting DNA into the cells. Full article

Spirocalcaridines A and B are among the most challenging members of the marine invertebrate-derived Leucetta alkaloids. Approaches to the construction and elaboration of the highly compact spirocyclic core are described. The synthesis of tricyclic guanidine via tandem oxidative amination dearomatizing spirocyclization (TOADS) using hypervalent iodine set the stage for total synthesis via the migration of the C4/C8 double bond to the C4/C5 position, followed by oxidation. The undesired but not surprising propensity of the spirocyclic cyclohexadienone to undergo rearrangement to the phenol hindered the desired olefin migration. Furthermore, initial efforts to install the oxidation sequentially, first at C5 and then at C4 in the complete carbon skeleton, were fraught with unforeseen challenges and unusual outcomes. In addition, the scope and limitations of hypervalent iodine-mediated tandem oxidative dearomatizing spirocyclization on various substrates were explored. Urethanes and thiourethanes underwent spirocyclization with an excellent yield, whereas the reaction with allylic substrates and species lacking the p-methoxy substituent did not proceed. Attempts to prepare other guanidine precursors are briefly discussed. Full article