Collection and transportation of SARS-CoV-2 and influenza A virus diagnostic samples: Optimizing the usage of guanidine-based chaotropic salts for enhanced biosafety and viral genome preservation.

Many virus lysis/transport buffers used in molecular diagnostics, including the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, contain guanidine-based chaotropic salts, primarily guanidine hydrochloride (GuHCl) or guanidine isothiocyanate (GITC). Although the virucidal effects of GuHCl and GITC alone against some enveloped viruses have been established, standardized data on their optimum virucidal concentrations against SARS-CoV-2 and effects on viral RNA stability are scarce. Thus, we aimed to determine the optimum virucidal concentrations of GuHCl and GITC against SARS-CoV-2 compared to influenza A virus (IAV), another enveloped respiratory virus. We also evaluated the effectiveness of viral RNA stabilization at the determined optimum virucidal concentrations under high-temperature conditions (35°C) using virus-specific real-time reverse transcription polymerase chain reaction. Both viruses were potently inactivated by 1.0 M GITC and 2.5 M GuHCl, but the GuHCl concentration for efficient SARS-CoV-2 inactivation was slightly higher than that for IAV inactivation. GITC showed better viral RNA stability than GuHCl at the optimum virucidal concentrations. An increased concentration of GuHCl or GITC increased viral RNA degradation at 35°C. Our findings highlight the need to standardize GuHCl and GITC concentrations in virus lysis/transport buffers and the potential application of these guanidine-based salts alone as virus inactivation solutions in SARS-CoV-2 and IAV molecular diagnostics.

Bioactivity of selenium-containing pyridinium salts: Prospecting future pharmaceutical constituents to treat liver diseases involving oxidative stress.

Redox imbalance leads to oxidative stress that causes irreversible cellular damage. The incorporation of the antioxidant element selenium (Se) in the structure of pyridinium salts has been used as a strategy in chemical synthesis and can be useful in drug development. We investigated the antioxidant activity of Se-containing pyridinium salts (named Compounds 3A, 3B, and 3C) through in vitro tests. We focused our study on liver protein carbonylation, liver lipoperoxidation, free radical scavenging activity (1,1-diphenyl-2-picryl-hydrazil [DPPH]; 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid [ABTS]), and enzyme-mimetic activity assays (glutathione S-transferase [GST]-like; superoxide dismutase [SOD]-like). In addition, 2-(4-chlorophenyl)-2-oxoethyl)-2-((phenylselanyl)methyl)pyridin-1-ium bromide (3C) was selected to evaluate the acute oral toxicity in mice due to the best antioxidant profile. The three compounds were effective in reducing the levels of protein carbonylation and lipoperoxidation in the liver in a µM concentration range. All compounds demonstrated scavenger activity of DPPH and ABTS radicals, and GST-like action. No significant effects were detected in the SOD-like assay. Experimental data also showed that the acute oral treatment of mice with Compound 3C (50 and 300 mg/kg) did not cause mortality or change markers of liver and kidney functions. In summary, our findings reveal the antioxidant potential of Se-containing pyridinium salts in liver tissue, which could be related to their radical scavenging ability and mimetic action on the GST enzyme. They also demonstrate a low toxicity potential for Compound 3C. Together, the promising results open space for future studies on the therapeutic application of these molecules.

Counterion influence on near-infrared-II heptamethine cyanine salts for photothermal therapy.

Photothermal therapy (PTT) has attracted extensive attention in cancer treatment. Heptamethine cyanine dyes with near-infrared (NIR) absorption performance have been investigated for PTT. However, they are often accompanied by poor photostability, suboptimal photothermal conversion and limited therapeutic efficacy. The photophysical properties of fluorescent organic salts can be tuned through counterion pairing. However, whether the counterion can influence the photostability and photothermal properties of heptamethine cyanine salts has not been clarified. In this work, we investigated the effects of eleven counter anions on the physical and photothermal properties of NIR-II heptamethine cyanine salts with the same heptamethine cyanine cation. The anions have great impacts on the physiochemical properties of dyes in solution including aggregation, photostability and photothermal conversion efficiency. The physical tuning enables the control over the cytotoxicity and phototoxicity of the dyes. The selected salts have been demonstrated to significantly suppress 4T1 breast tumor growth with low toxicity. The findings that the counterion has great effects on the photothermal properties of cationic NIR-II heptamethine cyanine dyes will provide a reference for the preparation of improved photothermal agents through counterion pairing with possible translation to humans.

Design, synthesis and bactericidal activity of novel coumarin derivatives containing pyridinium salts.

Coumarin is a natural product known for its diverse biological activities. While its antifungal properties in agricultural chemistry have been extensively studied, there is limited research on its antibacterial potential. In this study, we developed several novel coumarin derivatives by combining coumarin with pyridinium salt through molecular hybridization and chemical synthesis. Our findings reveal that most of these derivatives exhibit promising antibacterial activity. Among them, derivative A25 has been identified as the most effective compound based on three-dimensional quantitative structure-activity relationships. It demonstrates significant in vitro and in vivo activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicola (Xoc), and Xanthomonas campestris pv. citri (Xac), outperforming the commercially available thiediazole copper. Initial investigations into its mechanism of action suggest that A25 disrupts the cell membranes of Xoc and Xoo, thereby inhibiting bacterial growth. Additionally, A25 enhances the activity of defense enzymes in rice and modulates the expression of proteins related to the pyruvate metabolism pathway. This dual action contributes to rice's resistance against bacterial infestation. We anticipate that this study will serve as a foundation for the development of coumarin-based bactericides.

Mechanical properties of simulated dentin caries treated with metal cations and L-ascorbic acid 2-phosphate.

This pH cycling study aimed to investigate the effects of L-Ascorbic acid 2-phosphate (AA2P) salts of Mg, Zn, Mn, Sr, and Ba on the surface microhardness, compressive strength, diametral tensile strength (DTS), and solubility of root canal dentin. 186 cylindrical dentin specimens from 93 teeth were fortified with optimal concentrations of AA2P salts of Mg (0.18 mM), Zn (5.3 µM), Mn (2.2 × 10-8 M), Sr (1.8 µM), and Ba (1.9 µM). Saline was used as the control group. These dentin specimens underwent a 3-day cycling process simulating dentin caries formation through repeated sequences of demineralization and remineralization. Surface microhardness at 100 and 500 µm depths (n = 10/subgroup), scanning electron microscopy (n = 3/group), compressive strength (n = 10/group), DTS (n = 6/group), and solubility (n = 5/group) tests were performed to analyze the dentin specimens. Data were analyzed using Kolmogorov-Smirnov, one-way ANOVA, and Post Hoc Tukey tests (p < 0.05). The control group had significantly lower microhardness at both depths (p < 0.001), reduced DTS (p = 0.001), decreased compressive strength (p < 0.001), and higher weight loss (p < 0.001) than all other groups. The Sr group had the highest compressive strength and microhardness among all the groups. The microhardness was significantly higher for the 500 µm depth than the 100 µm depth (p < 0.001), but the difference in microhardness between depths across groups was not significant (p = 0.211). All fortifying solutions provided some protection against artificial caries lesions. Therefore, these elements might have penetrated and reinforced the demineralized dentin against acid dissolution.

Oxolane Ammonium Salts (Muscarine-Like)-Synthesis and Microbiological Activity.

Commercially available 2-deoxy-D-ribose was used to synthesize the appropriate oxolane derivative-(2R,3S)-2-(hydroxymethyl)oxolan-3-ol-by reduction and dehydration/cyclization in an acidic aqueous solution. Its monotosyl derivative, as a result of the quaternization reaction, allowed us to obtain eight new muscarine-type derivatives containing a quaternary nitrogen atom and a hydroxyl group linked to the oxolane ring. Their structure was fully confirmed by the results of NMR, MS and IR analyses. The crystal structure of the pyridinium derivative showed a high similarity of the conformation of the oxolane ring to previously published crystal structures of muscarine. Two reference strains of Gram-negative bacteria (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853), two reference strains of Gram-positive staphylococci (Staphylococcus aureus ATCC 25923 and Staphylococcus aureus ATCC 29213) and four reference strains of pathogenic yeasts of the genus Candida spp. (Candida albicans SC5314, Candida glabrata DSM 11226, Candida krusei DSM 6128 and Candida parapsilosis DSM 5784) were selected for the evaluation of the antimicrobial potential of the synthesized compounds. The derivative containing the longest (decyl) chain attached to the quaternary nitrogen atom turned out to be the most active.

Synthesis, Electronic, and Antibacterial Properties of 3,7-Di(hetero)aryl-substituted Phenothiazinyl N-Propyl Trimethylammonium Salts.

In this study, a library of 3,7-di(hetero)aryl-substituted 10-(3-trimethylammoniumpropyl)10H-phenothiazine salts is prepared. These title compounds and their precursors are reversible redox systems with tunable potentials. The Hammett correlation gives a very good correlation of the first oxidation potentials with σp parameters. Furthermore, the title compounds and their precursors are blue to green-blue emissive. Screening of the salts reveals for some derivatives a distinct inhibition of several pathogenic bacterial strains (Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli, Aconetobacter baumannii, and Klebsiella pneumoniae) in the lower micromolar range.

Exploring the Antitumor Efficacy of N-Heterocyclic Nitrilotriacetate Oxidovanadium(IV) Salts on Prostate and Breast Cancer Cells.

The crystal structures of two newly synthesized nitrilotriacetate oxidovanadium(IV) salts, namely [QH][VO(nta)(H2O)](H2O)2 (I) and [(acr)H][VO(nta)(H2O)](H2O)2 (II), were determined. Additionally, the cytotoxic effects of four N-heterocyclic nitrilotriacetate oxidovanadium(IV) salts-1,10-phenanthrolinium, [(phen)H][VO(nta)(H2O)](H2O)0.5 (III), 2,2'-bipyridinium [(bpy)H][VO(nta)(H2O)](H2O) (IV), and two newly synthesized compounds (I) and (II)-were evaluated against prostate cancer (PC3) and breast cancer (MCF-7) cells. All the compounds exhibited strong cytotoxic effects on cancer cells and normal cells (HaCaT human keratinocytes). The structure-activity relationship analysis revealed that the number and arrangement of conjugated aromatic rings in the counterion had an impact on the antitumor effect. The compound (III), the 1,10-phenanthrolinium analogue, exhibited the greatest activity, whereas the acridinium salt (II), with a different arrangement of three conjugated aromatic rings, showed the lowest toxicity. The increased concentrations of the compounds resulted in alterations to the cell cycle distribution with different effects in MCF-7 and PC3 cells. In MCF-7 cells, compounds I and II were observed to block the G2/M phase, while compounds III and IV were found to arrest the cell cycle in the G0/G1 phase. In PC3 cells, all compounds increased the rates of cells in the G0/G1 phase.

An inhibitory mechanism for suppressing high salt intake in Drosophila.

High concentrations of dietary salt are harmful to health. Like most animals, Drosophila melanogaster are attracted to foods that have low concentrations of salt, but show strong taste avoidance of high salt foods. Salt in known on multiple classes of taste neurons, activating Gr64f sweet-sensing neurons that drive food acceptance and 2 others (Gr66a bitter and Ppk23 high salt) that drive food rejection. Here we find that NaCl elicits a bimodal dose-dependent response in Gr64f taste neurons, which show high activity with low salt and depressed activity with high salt. High salt also inhibits the sugar response of Gr64f neurons, and this action is independent of the neuron's taste response to salt. Consistent with the electrophysiological analysis, feeding suppression in the presence of salt correlates with inhibition of Gr64f neuron activity, and remains if high salt taste neurons are genetically silenced. Other salts such as Na2SO4, KCl, MgSO4, CaCl2, and FeCl3 act on sugar response and feeding behavior in the same way. A comparison of the effects of various salts suggests that inhibition is dictated by the cationic moiety rather than the anionic component of the salt. Notably, high salt-dependent inhibition is not observed in Gr66a neurons-response to a canonical bitter tastant, denatonium, is not altered by high salt. Overall, this study characterizes a mechanism in appetitive Gr64f neurons that can deter ingestion of potentially harmful salts.

New Insights into the Phototoxicity of Anthracene-Based Chromophores: The Chloride Salt Effect†.

Unraveling the causes underlying polycyclic aromatic hydrocarbon phototoxicity is an essential step in understanding the harmful effects of these compounds in nature. Toward this end, we have studied the DNA interactions and photochemistry of N1-(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride in the presence and absence of NaF, KF, NaCl, KCl, NaBr, KBr, NaI, and KI (350 nm hν, pH 7.0). Exposing pUC19 plasmid to UV light in solutions containing 400 mM KCl formed significantly more direct strand breaks in DNA compared to no-salt control reactions. In contrast, NaCl increased DNA damage moderately, while the sodium(I) and potassium(I) fluoride, bromide, and iodide salts generally inhibited cleavage (I- > Br- > F-). A halide anion-induced heavy-atom effect was indicated by monitoring anthracene photodegradation and by employing the hydroxyl radical (•OH) probe hydroxyphenyl fluorescein (HPF). These studies revealed that among no-salt controls and the eight halide salts, only NaCl and KCl enabled the anthracene to photosensitize the production of high levels of DNA-damaging reactive oxygen species (ROS). Pre-irradiation of N1-(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride at 350 nm increased the amounts of chloride salt-induced •OH detected by HPF in subsequent anthracene photoactivation experiments. Taking into consideration that •OH and other highly reactive ROS are extremely short-lived, this result suggests that the pre-irradiation step might lead to the formation of oxidized anthracene photoproducts that are exceedingly redox-active. The fluorometric probes HPF and Singlet Oxygen Sensor Green revealed that KCl concentrations ranging from 150 to 400 mM and from 100 to 400 mM, respectively, enhanced N1-(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride photosensitized •OH and singlet oxygen (1O2) production over no-salt controls. Considering the relatively high levels of Na+, K+, and Cl- ions that exist in the environment and in living organisms, our findings may be relevant to the phototoxic effects exhibited by anthracenes and other polycyclic hydrocarbons in vivo.

Antimicrobial dichloroisocyanurate-salts for controlled release of chlorine.

Sodium dichloroisocyanurate (Na-DCC), a disinfectant known for rapid decomposition in water, loses its effectiveness with complete release of free available chlorine (FAC) in under an hour. To overcome this, a series of chlorine rich transition metal complexes/tetrabutylammonium (TBA) salts of DCC, including 2Na[Cu(DCC)4], 2Na[Fe(DCC)4], 2Na[Co(DCC)4]·6H2O, 2Na[Ni(DCC)4]·6H2O, and TBA[DCC]·4H2O have been developed for extended chlorine release studies. The DCC-salts are synthesized based on the metathesis reaction process and are characterized using IR, NMR, CHN analyses, TGA,DSC, and Lovi bond colorimeter. The DCC-salts displayed poor water solubility and low decomposition chlorine release profile compared to Na-DCC. The water solubility of DCC-salts was reduced by a factor of 5.37 to 2500 compared to Na-DCC. The decomposition release of FAC from DCC-salts has been studied over time in comparison to Na-DCC in distilled water using a Lovi-bond colorimeter. DCC-salts displayed controlled FAC release profiles that varied from 1-13 days depending on the type of metal/TBA unit in them, whereas the parent Na-DCC displayed complete FAC release in about 0.91 h. For a proof of concept, the controlled release of metal from one of the DCC-metal complex salts, i.e., copper from the Cu-DCC is also investigated with a function of time in distilled water at RT. The 100% release of copper from Cu-DCC was identified over a period of 10 days. In addition, the applicability of DCC-salts as excellent antiviral agents against the bacteriophage T4 and antibacterial agents against Erwinia, Pseudomonas aeruginosa PA014 (Gram-negative), and Staphylococcus epidermidis (Gram-positive) compared to Na-DCC has been demonstrated.

Vinyl functionalized 5,6-dimethylbenzimidazolium salts: Synthesis and biological activities.

A series of vinyl functionalized 5,6-dimethylbenzimidazolium salts are synthesized. All compounds were fully characterized by elemental analyses, MS, 1 H-NMR, 13 C-NMR, and IR spectroscopy techniques. Enzyme inhibition is a very active area of research in drug design and development. In this study, the synthesized novel benzimidazolium salts were evaluated toward the human erythrocyte carbonic anhydrase I (hCA I), and II (hCA II) isoenzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. They demonstrated highly potent inhibition ability against hCA I with Ki values of 484.8 ± 62.6-1389.7 ± 243.2 nM, hCA II with Ki values of 298.9 ± 55.7-926.1 ± 330.0 nM, α-glycosidase with Ki values of 170.3 ± 27-760.1 ± 269 µM, AChE with Ki values of 27.1 ± 3-77.6 ± 1.7 nM, and BChE with Ki values of 21.0 ± 5-61.3 ± 15 nM. As a result, novel vinyl functionalized 5,6-dimethylbenzimidazolium salts (1a-g) exhibited effective inhibition profiles toward studied metabolic enzymes. Therefore, we believe that these results may contribute to the development of new drugs particularly to treat some global disorders including glaucoma, Alzheimer's disease, and diabetes.

Acetylphenyl-substituted imidazolium salts: synthesis, characterization, in silico studies and inhibitory properties against some metabolic enzymes.

Herein, we present how to synthesize thirteen new 1-(4-acetylphenyl)-3-alkylimidazolium salts by reacting 4-(1-H-imidazol-1-yl)acetophenone with a variety of benzyl halides that contain either electron-donating or electron-withdrawing groups. The structures of the new imidazolium salts were conformed using different spectroscopic methods (1H NMR, 13C NMR, 19F NMR, and FTIR) and elemental analysis techniques. Furthermore, these compounds' the carbonic anhydrase (hCAs) and acetylcholinesterase (AChE) enzyme inhibition activities were investigated. They showed a highly potent inhibition effect toward AChE and hCAs with Ki values in the range of 8.30 ± 1.71 to 120.77 ± 8.61 nM for AChE, 16.97 ± 2.04 to 84.45 ± 13.78 nM for hCA I, and 14.09 ± 2.99 to 69.33 ± 17.35 nM for hCA II, respectively. Most of the synthesized imidazolium salts appeared to be more potent than the standard inhibitor of tacrine (TAC) against AChE and Acetazolamide (AZA) against CA. In the meantime, to prospect for potential synthesized imidazolium salt inhibitor(s) against AChE and hCAs, molecular docking and an ADMET-based approach were exerted.

Benzimidazolium Salts Bearing Nitrile Moieties: Synthesis, Enzyme Inhibition Profiling, and Molecular Docking Analysis for Carbonic Anhydrase and Acetylcholinesterase.

This report presents the synthesis and characterization of a range of benzimidazolium salts featuring 3-cyanopropyl groups on the 1st nitrogen atom and varied alkyl groups on the 3rd nitrogen atom within the benzimidazole structure. Benzimidazolium salts were synthesized by N-alkylation of 1-alkyl benzimidazole with 3-cyanopropyl-bromide. The new salts were characterized by 1 H and 13 C-NMR, FT-IR spectroscopic and elemental analysis techniques. In this study, the enzyme inhibition abilities of seven nitrile substituted benzimidazolium salts were investigated against acetylcholinesterase (AChE) and carbonic anhydrase isoenzymes I and II (hCA I and hCA II). They showed a highly potent inhibition effect on AChE, hCA I and hCA II (Ki values are in the range of 26.71-119.09 nM for AChE, 19.77 to 133.68 nM for hCA I and 13.09 to 266.38 nM for hCA II). Reflecting the binding mode of the synthesized cyanopropyl series, the importance of the 2,3,5,6-tetramethylbenzyl, 3-methylbenzyl and 3-benzyl groups for optimal interactions with target proteins, evaluated by molecular docking studies. At the same time, the docking findings support the inhibition constants (Ki ) values of the related compounds in this study. Potential compounds were also evaluated by their pharmacokinetic properties were predicted.

Biological Consequences of Vanadium Effects on Formation of Reactive Oxygen Species and Lipid Peroxidation.

Lipid peroxidation (LPO), a process that affects human health, can be induced by exposure to vanadium salts and compounds. LPO is often exacerbated by oxidation stress, with some forms of vanadium providing protective effects. The LPO reaction involves the oxidation of the alkene bonds, primarily in polyunsaturated fatty acids, in a chain reaction to form radical and reactive oxygen species (ROS). LPO reactions typically affect cellular membranes through direct effects on membrane structure and function as well as impacting other cellular functions due to increases in ROS. Although LPO effects on mitochondrial function have been studied in detail, other cellular components and organelles are affected. Because vanadium salts and complexes can induce ROS formation both directly and indirectly, the study of LPO arising from increased ROS should include investigations of both processes. This is made more challenging by the range of vanadium species that exist under physiological conditions and the diverse effects of these species. Thus, complex vanadium chemistry requires speciation studies of vanadium to evaluate the direct and indirect effects of the various species that are present during vanadium exposure. Undoubtedly, speciation is important in assessing how vanadium exerts effects in biological systems and is likely the underlying cause for some of the beneficial effects reported in cancerous, diabetic, neurodegenerative conditions and other diseased tissues impacted by LPO processes. Speciation of vanadium, together with investigations of ROS and LPO, should be considered in future biological studies evaluating vanadium effects on the formation of ROS and on LPO in cells, tissues, and organisms as discussed in this review.

Efficacy of Novel Quaternary Ammonium and Phosphonium Salts Differing in Cation Type and Alkyl Chain Length against Antibiotic-Resistant Staphylococcus aureus.

Antibacterial resistance poses a critical public health threat, challenging the prevention and treatment of bacterial infections. The search for innovative antibacterial agents has spurred significant interest in quaternary heteronium salts (QHSs), such as quaternary ammonium and phosphonium compounds as potential candidates. In this study, a library of 49 structurally related QHSs was synthesized, varying the cation type and alkyl chain length. Their antibacterial activities against Staphylococcus aureus, including antibiotic-resistant strains, were evaluated by determining minimum inhibitory/bactericidal concentrations (MIC/MBC) ≤ 64 µg/mL. Structure-activity relationship analyses highlighted alkyl-triphenylphosphonium and alkyl-methylimidazolium salts as the most effective against S. aureus CECT 976. The length of the alkyl side chain significantly influenced the antibacterial activity, with optimal chain lengths observed between C10 and C14. Dose-response relationships were assessed for selected QHSs, showing dose-dependent antibacterial activity following a non-linear pattern. Survival curves indicated effective eradication of S. aureus CECT 976 by QHSs at low concentrations, particularly compounds 1e, 3e, and 5e. Moreover, in vitro human cellular data indicated that compounds 2e, 4e, and 5e showed favourable safety profiles at concentrations ≤ 2 µg/mL. These findings highlight the potential of these QHSs as effective agents against susceptible and resistant bacterial strains, providing valuable insights for the rational design of bioactive QHSs.

Research Advances on the Bioactivity of 1,2,3-Triazolium Salts.

1,2,3-Triazolium salts have demonstrated significant potential in the fields of medicine and agriculture, exhibiting exceptional antibacterial, antifungal, anticancer, and antileishmanial properties. Moreover, these salts can be utilized as additives or components to produce nano- and fiber-based materials with antibacterial properties. In this review, we summarize several synthetic strategies to obtain 1,2,3-triazolium salts and the structures of 1,2,3-triazolium derivatives with biological activities in the domains of pharmaceuticals, pesticides, and functional materials. Additionally, the structure-activity relationship (SAR) of 1,2,3-triazolium salts with different biological activities has been analyzed. Finally, this review presents the potential applications and prospects of 1,2,3-triazolium salts in the fields of agriculture, medicine, and industrial synthesis.

Fluoroquinolone-Based Organic Salts (GUMBOS) with Antibacterial Potential.

Antimicrobial resistance is a silent pandemic considered a public health concern worldwide. Strategic therapies are needed to replace antibacterials that are now ineffective. One approach entails the use of well-known antibacterials along with adjuvants that possess non-antibiotic properties but can extend the lifespan and enhance the effectiveness of the treatment, while also improving the suppression of resistance. In this regard, a group of uniform materials based on organic salts (GUMBOS) presents an alternative to this problem allowing the combination of antibacterials with adjuvants. Fluoroquinolones are a family of antibacterials used to treat respiratory and urinary tract infections with broad-spectrum activity. Ciprofloxacin and moxifloxacin-based GUMBOS were synthesized via anion exchange reactions with lithium and sodium salts. Structural characterization, thermal stability and octanol/water partition ratios were evaluated. The antibacterial profiles of most GUMBOS were comparable to their cationic counterparts when tested against Gram-positive S. aureus and Gram-negative E. coli, except for deoxycholate anion, which demonstrated the least effective antibacterial activity. Additionally, some GUMBOS were less cytotoxic to L929 fibroblast cells and non-hemolytic to red blood cells. Therefore, these agents exhibit promise as an alternative approach to combining drugs for treating infections caused by resistant bacteria.

First Synthesis of DBU-Conjugated Cationic Carbohydrate Derivatives and Investigation of Their Antibacterial and Antifungal Activity.

The emergence of drug-resistant bacteria and fungi represents a serious health problem worldwide. It has long been known that cationic compounds can inhibit the growth of bacteria and fungi by disrupting the cell membrane. The advantage of using such cationic compounds is that the microorganisms would not become resistant to cationic agents, since this type of adaptation would mean significantly altering the structure of their cell walls. We designed novel, DBU (1,8-diazabicyclo[5.4.0]undec-7-ene)-derived amidinium salts of carbohydrates, which may be suitable for disturbing the cell walls of bacteria and fungi due to their quaternary ammonium moiety. A series of saccharide-DBU conjugates were prepared from 6-iodo derivatives of d-glucose, d-mannose, d-altrose and d-allose by nucleophilic substitution reactions. We optimized the synthesis of a d-glucose derivative, and studied the protecting group free synthesis of the glucose-DBU conjugates. The effect of the obtained quaternary amidinium salts against Escherichia coli and Staphylococcus aureus bacterial strains and Candida albicans yeast was investigated, and the impact of the used protecting groups and the sugar configuration on the antimicrobial activity was analyzed. Some of the novel sugar quaternary ammonium compounds with lipophilic aromatic groups (benzyl and 2-napthylmethyl) showed particularly good antifungal and antibacterial activity.

Benzoquinoline Derivatives: An Attractive Approach to Newly Small Molecules with Anticancer Activity.

This study presents the synthesis, structural characterization, and in vitro evaluation of anticancer activity of some newly benzo[f]quinoline derivatives. The synthesis is facile and efficient, involving two steps: quaternization of nitrogen heterocycle followed by a [3+2] dipolar cycloaddition reaction. The synthesized compounds were characterized by FTIR, NMR, and X-ray diffraction on monocrystal in the case of compounds 6c and 7c. An in vitro single-dose anticancer assay of eighteen benzo[f]quinoline compounds, quaternary salts, and cycloadducts, was performed. The results showed that the most active compounds were quaternary salts 3d and 3f with aromatic R substituents. Quaternary salt 3d revealed non-selective activity against all types of cancer cells, while salt 3f exhibited a highly selective activity against leukemia cells. Compound 3d also presented remarkable cytotoxic efficiency against four distinct types of cancer cells-namely, non-small cell lung cancer HOP-92, melanoma LOX IMVI, melanoma SK-MEL-5, and breast cancer MDA-MB-468. Compound 3f was selected for five-dose screening. The study also includes SAR correlations.