Antitumor activity of lower rim amino derivatives of thiacalixarene

© 2020 Author(s). Dependence of cytotoxicity of lower-rim substituted aminoalkoxythiacalix[4]arenes towards normal and tumor cell lines on the distance from receptor amino group to the macrocyclic scaffold, as well as the oxidation state of nitrogen atom has been determined

Stevioside Has the Maximum Biological Activity among Natural Stevia Diterpenes

© 2020, Pleiades Publishing, Ltd. Abstract: The concentrations of steviol and its derivatives stimulating the growth of wheat plants were measured: 10–8 for stevioside and 10–9 М for steviol and isosteviol. It was found that stevioside increased the activity of amylolytic enzymes and protein content, as well as frost tolerance of the roots of wheat seedlings. Thus, stevioside can be recommended for the development of complex phytopreparations for stimulating the growth processes and increasing the resistance of wheat plants to low temperatures

Design and synthesis of amphiphilic 2-hydroxybenzylphosphonium salts with antimicrobial and antitumor dual action

© 2020 Elsevier Ltd Here we report the synthesis and biological evaluation of a series of new 2-hydroxybenzylphosphonium salts (QPS) with antimicrobial and antitumor dual action. The most active compounds exhibit antimicrobial activity at a micromolar level against Gram-positive bacteria Sa (ATCC 209p and clinical isolates), Bc (1–2 μM) and fungi Tm and Ca, and induced no notable hemolysis at MIC. The change in nature of substituents of the same length led to a drastic change of biological activity. Self-assembly behavior of the octadecyl and oleyl derivatives was studied. QPS demonstrated self-assembly within the micromolar range with the formation of nanosized aggregates capable of the solubilizing hydrophobic probe. The synthesized phosphonium salts were tested for cytotoxicity. The most potent salt was active against on M−Hela cell line with IC50 on the level of doxorubicin and good selectivity. According to the cytofluorimetry analysis, the salts induced mitochondria-dependent apoptosis

The construction of supramolecular and hybrid Ag-AgCl nanoparticles with photodynamic therapy action on the base of tetraundecylсalix[4]resorcinarene-mPEG conjugate

The development of new nanomaterials with therapeutic potential is a modern task due to their outstanding properties and promising effectiveness. Here the usage of acylhydrazone bond-based сalix[4]resorcinarene-mPEG conjugate (C11-mPEG) in the formation of both supramolecular and hybrid nanoparticles with in vitro photodynamic therapy (PDT) activity is described. C11-mPEG is hydrolyzed with a decrease in pH of solution; the conjugate and its degradation product have the low hemolytic activity and low cytotoxicity against normal cells. The self-association of the conjugate was studied in the aqueous solutions with pH 7.4 and 5. C11-mPEG forms self-associates that serve as pH-sensitive supramolecular nanocontainers for photosensitizer Methylene Blue (MB). In the in vitro PDT experiment the stronger decrease of tumor cells (M-Hela cells) viability in the presence of encapsulated MB is observed in comparison with free MB. Also C11-mPEG acts as a stabilizing agent for Ag@AgCl nanoparticles, which were obtained with 5/1 and 2/1 Ag+/C11-mPEG molar ratio and different reducing agents (sodium borohydride and hydrazine hydrate). The stronger cytotoxicity of hybrid NPs against tumor cells in comparison with normal was shown. Further it was found that the irradiation of the hybrid nanoparticles at 630 nm leads to the sharp increase in their cytotoxicity against M-Hela cells. The high level of ROS formation in the cells in the presence of both supramolecular and hybrid NPs under in vitro PDT experiment was determined

Doxorubicin delivery by polymer nanocarrier based on N-methylglucamine resorcinarene

© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group. Herein we describe a simple method for the synthesis of polymer nanocarrier for the doxorubicin delivery. The nanocarrier consists of N-methyl-glucamine resorcinarenes that are covalently bound to phenylboronic acid. The nanocarrier is stable at normal pH but is hydrolysed at pH below 6. It demonstrates low cytotoxicity and haemolytic activity. Doxorubicin was successfully loaded into the nanocarriers cavity and its release occurs at pH. Flow cytometry data showed that the carrier improves the penetration of doxorubicin into M-Hela cancer cell lines. The encapsulated doxorubicin demonstrates higher cytotoxicity towards the cancer cells

A novel salt-responsive hydrogel on the base of calixresorcinarene–mPEG amide conjugate

A novel low toxic amide calix[4]resorcinarene–mPEG conjugates of amphiphilic and dendrimeric character were synthesized. It was shown that the growth of the temperature or the ionic strength growth of the solution leads to different demonstration of the amplification of hydrophobic interactions in the conjugates self-associates. It was found that in PBS or 0.9 % NaCl solutions the amphiphilic conjugate form micellar solution, and the dendrimeric conjugate – hydrogel, which is capable of the reversible sol-gel transition. It was shown by DSC analysis that the dendrimeric conjugate binds of 15 % of water molecules in an aqueous solution (non-freezing bound water), but in the salt solution the conjugate-water interaction is practically absent. This leads to the additional self-aggregation of conjugate molecules and to the gel formation. The high degree of substrate sorption by the hydrogel (Methylene Blue, encapsulation effectiveness is 78 %) and its reversible binding-release by the regulation of the solution ionic strength have been demonstrated

Ammonium-Charged Sterically Hindered Phenols with Antioxidant and Selective Anti-Gram-Positive Bacterial Activity

© 2020 Wiley-VHCA AG, Zurich, Switzerland The increase in the resistance of pathogens, in particular Staphylococcus aureus, to the action of antibiotics necessitates the search for new readily available and non-toxic drugs. In solving this problem, phenolic acylhydrazones have high potential. In this communication, the synthesis of quaternary ammonium compounds containing a differently substituted phenolic moiety has been performed. An initial study of antimicrobial activity showed that these compounds are highly selective against S. aureus and B. cereus. The highest activity (MIC 2.0 μm) was shown by hydrazones containing a catechol fragment. These compounds are more than 3-fold more active against S. aureus and 3–10-fold more active against B. cereus than norfloxacin. Low hemolytic and high antioxidant activities of all new compounds were also established

Polymer–colloid complexes based on cationic imidazolium amphiphile, polyacrylic acid and dna decamer

The solution behavior and physicochemical characteristics of polymer–colloid complexes based on cationic imidazolium amphiphile with a dodecyl tail (IA-12) and polyacrylic acid (PAA) or DNA decamer (oligonucleotide) were evaluated using tensiometry, conductometry, dynamic and electrophoretic light scattering and fluorescent spectroscopy and microscopy. It has been established that PAA addition to the surfactant system resulted in a ca. 200-fold decrease in the aggregation threshold of IA-12, with the hydrodynamic diameter of complexes ranging within 100–150 nm. Electrostatic forces are assumed to be the main driving force in the formation of IA-12/PAA complexes. Factors influencing the efficacy of the complexation of IA-12 with oligonucleotide were determined. The nonconventional mode of binding with the involvement of hydrophobic interactions and the intercalation mechanism is probably responsible for the IA-12/oligonucleotide complexation, and a minor contribution of electrostatic forces occurred. The latter was supported by zeta potential measurements and the gel electrophoresis technique, which demonstrated the low degree of charge neutralization of the complexes. Importantly, cellular uptake of the IA-12/oligonucleotide complex was confirmed by fluorescence microscopy and flow cytometry data on the example of M-HeLa cells. While single IA-12 samples exhibit roughly similar cytotoxicity, IA-12–oligonucleotide complexes show a selective effect toward M-HeLa cells (IC50 1.1 µM) compared to Chang liver cells (IC50 23.1 µM)

The pH-responsive calix[4]resorcinarene-mPEG conjugates bearing acylhydrazone bonds: Synthesis and study of the potential as supramolecular drug delivery systems

© 2020 Elsevier B.V. The synthesis of new conjugates of calix[4]resorcinarenes and methoxy-PEG via acylhydrazone bonds and their study in the formation of pH-sensitive low-toxic supramolecular drug delivery systems have described. The syntheses have been performed on the base of two calix[4]resorcinarenes in chair and boat conformations to obtain the dendrimer-like and amphiphilic conjugates, respectively. The structures of the conjugates have been confirmed by 1H, 13C NMR, and FT-IR spectroscopy, Maldi-TOF mass spectroscopy, and SLS method. The self-association of both amphiphilic and dendrimer-like conjugates has been found (NMR FT-PGSE, fluorimetry, DLS and TEM methods). The hydrolysis of the conjugates at pH 5.5 (proved by 1H NMR and FT-IR spectroscopy, DLS method) lead to the improved release of the conjugate-encapsulated Dox. The low hemolytic activity and low cytotoxicity against Chang liver cells of the conjugates and products of their hydrolysis have been demonstrated. Meanwhile, the improved cytotoxicity and photodynamic activity of conjugates-encapsulated drugs (Dox and Methylene Blue, respectively) has been found in vitro. The results have indicated the potential using of the calix[4]resorcinarene-mPEG conjugates bearing acylhydrazone bonds as supramolecular drug delivery systems

Terbium(III)-thiacalix[4]arene nanosensor for highly sensitive intracellular monitoring of temperature changes within the 303–313 K range

© 2020, The Author(s). The work introduces hydrophilic PSS-[Tb2(TCAn)2] nanoparticles to be applied as highly sensitive intracellular temperature nanosensors. The nanoparticles are synthesized by solvent-induced nanoprecipitation of [Tb2(TCAn)2] complexes (TCAn - thiacalix[4]arenes bearing different upper-rim substituents: unsubstituted TCA1, tert-buthyl-substituted TCA2, di- and tetra-brominated TCA3 and TCA4) with the use of polystyrenesulfonate (PSS) as stabilizer. The temperature responsive luminescence behavior of PSS-[Tb2(TCAn)2] within 293–333 K range in water is modulated by reversible changes derived from the back energy transfer from metal to ligand (M* → T1) correlating with the energy gap between the triplet levels of ligands and resonant 5D4 level of Tb3+ ion. The lowering of the triplet level (T1) energies going from TCA1 and TCA2 to their brominated counterparts TCA3 and TCA4 facilitates the back energy transfer. The highest ever reported temperature sensitivity for intracellular temperature nanosensors is obtained for PSS-[Tb2(TCA4)2] (SI = 5.25% K−1), while PSS-[Tb2(TCA3)2] is characterized by a moderate one (SI = 2.96% K−1). The insignificant release of toxic Tb3+ ions from PSS-[Tb2(TCAn)2] within heating/cooling cycle and the low cytotoxicity of the colloids point to their applicability in intracellular temperature monitoring. The cell internalization of PSS-[Tb2(TCAn)2] (n = 3, 4) marks the cell cytoplasm by green Tb3+-luminescence, which exhibits detectable quenching when the cell samples are heated from 303 to 313 K. The colloids hold unprecedented potential for in vivo intracellular monitoring of temperature changes induced by hyperthermia or pathological processes in narrow range of physiological temperatures