Brain tumor glioblastoma is one of the worst types of cancer. The blood-brain barrier prevents drugs from reaching brain cells and shields glioblastoma from treatment. The creation of nanocarriers to ...improve drug delivery and internalization effectiveness may be the solution to this issue. In this paper, we report on a new nanocarrier that was developed to deliver the anticancer drug doxorubicin to glioblastoma cells. The nanocarrier was obtained by nanoemulsion polymerization of diallyl disulfide with 1-allylthymine. Diallyl disulfide is a redox-sensitive molecule involved in redox cell activities, and thymine is a uracil derivative and one of the well-known bioactive compounds that can enhance the pharmacological activity of doxorubicin. Doxorubicin was successfully introduced into the nanocarrier with a load capacity of about 4.6%. Biological studies showed that the doxorubicin nanocarrier composition is far more cytotoxic to glioblastoma cells (T98G) than it is to cancer cells (M-HeLa) and healthy cells (Chang liver). The nanocarrier improves the penetration of doxorubicin into T98G cells and accelerates the cells' demise, as is evident from flow cytometry and fluorescence microscopy data. The obtained nanocarrier, in our opinion, is a promising candidate for further research in glioblastoma therapy.
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As a result of bright complexation properties, easy functionalization and the ability to self-organize in an aqueous solution, amphiphilic supramolecular macrocycles are being actively studied for ...their application in nanomedicine (drug delivery systems, therapeutic and theranostic agents, and others). In this regard, it is important to study their potential toxic effects. Here, the synthesis of amphiphilic calix4resorcinarene carboxybetaines and their esters and the study of a number of their microbiological properties are presented: cytotoxic effect on normal and tumor cells and effect on cellular and non-cellular components of blood (hemotoxicity, anti-platelet effect, and anticoagulant activity). Additionally, the interaction of macrocycles with bovine serum albumin as a model plasma protein is estimated by various methods (fluorescence spectroscopy, synchronous fluorescence spectroscopy, circular dichroic spectroscopy, and dynamic light scattering). The results demonstrate the low toxicity of the macrocycles, their anti-platelet effects at the level of acetylsalicylic acid, and weak anticoagulant activity. The study of BSA-macrocycle interactions demonstrates the dependence on macrocycle hydrophilic/hydrophobic group structure; in the case of carboxybetaines, the formation of complexes prevents self-aggregation of BSA molecules in solution. The present study demonstrates new data on potential drug delivery nanosystems based on amphiphilic calix4resorcinarenes for their cytotoxicity and effects on blood components.
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Structure-activity relationships are important for the design of biocides and sanitizers. During the spread of resistant strains of pathogenic microbes, insights into the correlation between ...structure and activity become especially significant. The most commonly used biocides are nitrogen-containing compounds; the phosphorus-containing ones have been studied to a lesser extent. In the present study, a broad range of sterically hindered quaternary phosphonium salts (QPSs) based on tri-
-butylphosphine was tested for their activity against Gram-positive (
,
) and Gram-negative (
,
) bacteria and fungi (
,
var. gypseum). The cation structure was confirmed to determine their biological activity. A number of QPSs not only exhibit high activity against both Gram-positive and -negative bacteria but also possess antifungal properties. Additionally, the hemolytic and cytotoxic properties of QPSs were determined using blood and a normal liver cell line, respectively. The results show that tri-
-butyl(
-dodecyl)phosphonium and tri-
-butyl(
-tridecyl)phosphonium bromides exhibit both low cytotoxicity against normal human cells and high antimicrobial activity against bacteria, including methicillin-resistant strains
(
). The mechanism of QPS action on microbes is discussed. Due to their high selectivity for pathogens, sterically hindered QPSs could serve as effective tunable biocides.
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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.
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A series of new 2-hydroxy-3-methoxybenzylidenethiazolo3,2-
pyrimidines with different aryl substituents at the 5 position are synthesized and characterized by
H/
C NMR and IR-spectroscopy and ...mass-spectrometry, as well as single crystal X-ray diffraction (SCXRD). It was demonstrated that the type of hydrogen bonding can play a key role in the chiral discrimination of these compounds in the crystalline phase. The hydrogen bond of the O-H...N type leads to 1D supramolecular heterochiral chains or conglomerate crystallization in the case of the formation of homochiral chains. The hydrogen bond of O-H...O type gave racemic dimers, which are packed into 2D supramolecular layers with a parallel or angular dimers arrangement. Halogen bonding of the N...Br or O...Br type brings a new motif into supramolecular self-assembly in the crystalline phase: the formation of 1D supramolecular homochiral chains instead 2D supramolecular layers. The study of cytotoxicity against various tumor cells in vitro was carried out. It was found that 2-hydroxy-3-methoxybenzylidenethiazolo3,2-
pyrimidines with 3-nitrophenyl substituent at C5 carbon atom demonstrated a high efficiency against M-HeLa (cervical adenocarcinoma) and low cytotoxicity against normal liver cells.
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A series of new thiazolo3,2-
pyrimidines different by aryl substituents in 2 and 5 positions are synthesized and characterized in solution as well as in the crystalline phase using
H and
C NMR-, ...IR-spectroscopies, mass-spectrometry methods, and single crystal X-ray diffraction (SCXRD). The SCXRD study revealed the role of intermolecular H-bonding in the formation of supramolecular architectures (racemic monomers, centrosymmetric racematic dimers, or homochiral 1D chains) of obtained thiazolo3,2-
pyrimidines derivatives depending on solvents (aprotic DMSO or protic EtOH) used upon the crystallization process. Moreover, the in vitro study of cytotoxicity toward different tumor cells showed their high or moderate efficiency with moderate cytotoxicity against normal liver cells which allows to consider the obtained thiazolo3,2-
pyrimidine derivatives as promising candidates for application as antitumor agents.
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Antimicrobial and cytotoxic activities of several ammonium derivatives of diterpenoids steviol and isosteviol have been investigated in vitro. The results have showed that these ...compounds possess high antibacterial activity against MRSA strains and cytotoxic effect against cancer cell lines MCF-7, M−HeLa, A-549, PC3, HepG2, T98G. Lead compounds 4 and 5 were detected, which, in the case of the MCF-7 cell line (human breast adenocarcinoma), showed IC50 at the doxorubicin level with a selectivity index of 5.0–5.2. Flow cytometry and laser confocal microscopy analysis demonstrated that the mechanism of cytotoxic effects of the tested compounds on MCF-7 cells could be associated with the induction of apoptosis along the mitochondrial pathway. At the same time, they did not cause hemolysis and showed only slight cytotoxicity with respect to normal human cells of embryonic lung (Wi-38).
The obtained results allow us to consider the studied compounds as promising scaffolds for the design of new effective antibacterial drugs and anticancer agents targeting mitochondria.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
It has been shown for a wide range of epoxy compounds that their interaction with triphenylphosphonium triflate occurs with a high chemoselectivity and leads to the formation of ...(2-hydroxypropyl)triphenylphosphonium triflates
substituted in the 3-position with an alkoxy, alkylcarboxyl group, or halogen, which were isolated in a high yield. Using the methodology for the disclosure of epichlorohydrin with alcohols in the presence of boron trifluoride etherate, followed by the substitution of iodine for chlorine and treatment with triphenylphosphine, 2-hydroxypropyltriphenylphosphonium iodides
were also obtained. The molecular and supramolecular structure of the obtained phosphonium salts was established, and their high antitumor activity was revealed in relation to duodenal adenocarcinoma. The formation of liposomal systems based on phosphonium salt
and
-α-phosphatidylcholine (PC) was employed for improving the bioavailability and reducing the toxicity. They were produced by the thin film rehydration method and exhibited cytotoxic properties. This rational design of phosphonium salts
and
has promising potential of new vectors for targeted delivery into mitochondria of tumor cells.
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A series of novel 4-(het)arylimidazoldin-2-ones were obtained by the acid-catalyzed reaction of (2,2-diethoxyethyl)ureas with aromatic and heterocyclic C-nucleophiles. The proposed approach to ...substituted imidazolidinones benefits from excellent regioselectivity, readily available starting materials and a simple procedure. The regioselectivity of the reaction was rationalized by quantum chemistry calculations and control experiments. The anti-cancer activity of the obtained compounds was tested in vitro.
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Novel cationic amphiphiles of the 3-alkyl-1-(4-methoxyphenyl)-1H-imidazol-3-ium bromide series bearing methoxyphenyl fragments (MPI-n) have been synthesized. Their aggregation properties in aqueous ...solutions, solubilization capacity, and hemolytic and antimicrobial activities have been investigated by a number of physicochemical methods. Using tensiometry, conductometry, and fluorescence spectroscopy, it was shown that the MPI-n have lower CMCs than their nonfunctionalized counterparts. The unusual alkyl-chain-length-dependent morphology of aggregates is testified for this homological series. Amphiphiles with 12, 14, and 16 alkyl tails are characterized by the formation of micellar aggregates, while a surfactant with a decyl tail is characterized by the formation of larger aggregates with lower surface curvature. The MPI-10 aggregate morphology was rationalized in terms of the packing parameter consideration and was supported by size measurements and the fluorescence probe techniques, which showed that vesicle-like aggregates in close-packing mode probably occur. MPI-n aggregates have exhibited a high solubilization capacity toward hydrophobic azo dye Orange OT. Importantly, amphiphiles studied showed (i) high bacteriostatic activity at the level of ciprofloxacin; (ii) high bactericidal action against all Gram-positive bacteria, including methicillin-resistant strains; (iii) bactericidal properties against Gram-negative bacteria; and (iv) low hemolytic activity.
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![Calix[4]Resorcinarene Carbo...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1422-0067_1661-6596/small "Calix[4]Resorcinarene Carboxybetaines and Carboxybetaine Esters: Synthesis, Investigation of In Vitro Toxicity, Anti-Platelet Effects, Anticoagulant Activity, and BSA Binding Affinities")
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