Targeting c-Myc with decoy oligodeoxynucleotide-loaded polycationic nanoparticles inhibits cell growth and induces apoptosis in cancer stem-like cells (NTERA-2).

BACKGROUND: An increase in cancer stem cell (CSC) populations and their resistance to common treatments could be a result of c-Myc dysregulations in certain cancer cells. In the current study, we investigated anticancer effects of c-Myc decoy ODNs loaded-poly (methacrylic acid-co-diallyl dimethyl ammonium chloride) (PMA-DDA)-coated silica nanoparticles as carriers on cancer-like stem cells (NTERA-2). METHODS AND RESULTS: The physicochemical characteristics of the synthesized nanocomposites (SiO2@PMA-DDA-DEC) were analyzed using FT-IR, DLS, and SEM techniques. UV-Vis spectrophotometer was applied to analyze the release pattern of decoy ODNs from the nanocomposite. Furthermore, uptake, cell viability, apoptosis, and cell cycle assays were used to investigate the anticancer effects of nanocomposites loaded with c-Myc decoy ODNs on NTERA-2 cancer cells. The results of physicochemical analytics demonstrated that SiO2@PMA-DDA-DEC nanocomposites were successfully synthesized. The prepared nanocomposites were taken up by NTERA-2 cells with high efficiency, and could effectively inhibit cell growth and increase apoptosis rate in the treated cells compared to the control group. Moreover, SiO2@PMA-DDA nanocomposites loaded with c-Myc decoy ODNs induced cell cycle arrest at the G0/G1 phase in the treated cells. CONCLUSIONS: The conclusion drawn from this study is that c-Myc decoy ODN-loaded SiO2@PMA-DDA nanocomposites can effectively inhibit cell growth and induce apoptosis in NTERA-2 cancer cells. Moreover, given that a metal core is incorporated into this synthetic nanocomposite, it could potentially be used in conjunction with irradiation as part of a decoy-radiotherapy combinational therapy in future investigations.

Sensing and Microbiological Activity of a New Blue Fluorescence Polyamidoamine Dendrimer Modified with 1,8-Naphthalimide Units.

A novel second-generation blue fluorescent polyamidoamine dendrimer peripherally modified with sixteen 4-N,N-dimethylaninoethyloxy-1,8-naphthalimide units was synthesized. Its basic photophysical characteristics were investigated in organic solvents of different polarity. It was found that in these solvents, the dendrimer is colorless and emitted blue fluorescence with different intensities depending on their polarity. The effect of the pH of the medium on the fluorescence intensity was investigated and it was found that in the acidic medium, the fluorescence is intense and is quenched in the alkaline medium. The ability of the dendrimer to detect metal ions (Pb2+, Zn2+, Mg2+, Sn2+, Ba2+, Ni2+, Sn2+, Mn2+, Co2+, Fe3+, and Al3+) was also investigated, and it was found that in the presence of Fe3+, the fluorescent intensity was amplified more than 66 times. The antimicrobial activity of the new compound has been tested in vitro against Gram-positive B. cereus and Gram-negative P. aeruginosa. The tests were performed in the dark and after irradiation with visible light. The antimicrobial activity of the compound enhanced after light irradiation and B. cereus was found slightly more sensitive than P. aeruginosa. The increase in antimicrobial activity after light irradiation is due to the generation of singlet oxygen particles, which attack bacterial cell membranes.

The selective extraction of dietary polyamines from chicken breast using the application of a lab-on-a-chip electromembrane and dispersive liquid-liquid microextraction followed by gas chromatography-mass spectrometry.

Excessive dietary polyamines (PAs), including putrescine (PUT), spermine (SPM), and spermidine (SPD), have become a worldwide concern due to their carcinogenicity and reduced shelf life. A modern miniaturized on-chip electromembrane extraction (EME) has been applied to extract these compounds from chicken breast samples. This method is based fundamentally on ionic compounds' electrostatic attraction, diffusion, and solubility in the acceptor phase. The chemical structure of polyamines enables their efficient extraction using an electric driving force on a microchip device. HCl solution (0.1 mol L-1) was applied as an aqueous acceptor solvent. Dispersive liquid-liquid microextraction was performed after EME to facilitate joining three-phase EME to GC-MS and improve the merit figures. The total ranges of 3.77-7.89 µg g-1, 3.48-7.02 µg g-1, and 0.78-2.20 µg g-1 were acquired as PUT, SPM and SPD concentrations in chicken breast, respectively. The results demonstrate that the level of PAs in fresh chicken breast samples is not concerning, but it may reduce the quality of chicken meat over time. This novel analytical technique has several advantages: high recovery, substantial quickness, remarkable selectivity, and good enrichment factors. This emerging method could be generalized to other studies to analyze different foodstuffs.

Chemical Versatility in Catalysis and Inhibition of the Class IIb Histone Deacetylases.

ConspectusThe zinc-dependent histone deacetylases (HDACs 1-11) belong to the arginase-deacetylase superfamily of proteins, members of which share a common α/ß fold and catalytic metal binding site. While several HDACs play a role in epigenetic regulation by catalyzing acetyllysine hydrolysis in histone proteins, the biological activities of HDACs extend far beyond histones. HDACs also deacetylate nonhistone proteins in the nucleus as well as the cytosol to regulate myriad cellular processes. The substrate pool is even more diverse in that certain HDACs can hydrolyze other covalent modifications. For example, HDAC6 is also a lysine decrotonylase, and HDAC11 is a lysine-fatty acid deacylase. Surprisingly, HDAC10 is not a lysine deacetylase but instead is a polyamine deacetylase. Thus, the HDACs are biologically and chemically versatile catalysts as they regulate the function of diverse protein and nonprotein substrates throughout the cell.Owing to their critical regulatory functions, HDACs serve as prominent targets for drug design. At present, four HDAC inhibitors are FDA-approved for cancer chemotherapy. However, these inhibitors are active against multiple HDAC isozymes, and a lack of selectivity is thought to contribute to undesirable side effects. Current medicinal chemistry campaigns focus on the development of isozyme-selective inhibitors, and many such studies largely focus on HDAC6 and HDAC10. HDAC6 is a target for therapeutic intervention due to its cellular role as a tubulin deacetylase and tau deacetylase, and selective inhibitors are being studied in cancer chemotherapy and the treatment of peripheral neuropathy. Crystal structures of enzyme-inhibitor complexes reveal how various features of inhibitor design, such as zinc-coordinating groups, bifurcated capping groups, and aromatic fluorination patterns, contribute to affinity and isozyme selectivity. The polyamine deacetylase HDAC10 is also an emerging target for cancer chemotherapy. Crystal structures of intact substrates trapped in the HDAC10 active site reveal the molecular basis of strikingly narrow substrate specificity for N8-acetylspermidine hydrolysis. Active site features responsible for substrate specificity have been successfully exploited in the design of potent and selective inhibitors.In this Account, I review the structural chemistry and inhibition of HDACs, highlighting recent X-ray crystallographic and functional studies of HDAC6 and HDAC10 in my laboratory. These studies have yielded fascinating snapshots of catalysis as well as novel chemical transformations involving bound inhibitors. The zinc-bound water molecule in the HDAC active site is the catalytic nucleophile in the deacetylation reaction, but this activated water molecule can also react with inhibitor C═O or C═N groups to yield unanticipated reaction products that bind exceptionally tightly. Versatile active site chemistry unleashes the full inhibitory potential of such compounds, and X-ray crystallography allows us to view this chemistry in action.

Trehalose-polyamine/DNA nanocomplexes: impact of vector architecture on cell and organ transfection selectivity.

A novel family of precision-engineered gene vectors with well-defined structures built on trehalose and trehalose-based macrocycles (cyclotrehalans) comprising linear or cyclic polyamine heads have been synthesized through procedures that exploit click chemistry reactions. The strategy was conceived to enable systematic structural variations and, at the same time, ensuring that enantiomerically pure vectors are obtained. Notably, changes in the molecular architecture translated into topological differences at the nanoscale upon co-assembly with plasmid DNA, especially regarding the presence of regions with short- or long-range internal order as observed by TEM. In vitro and in vivo experiments further evidenced a significant impact on cell and organ transfection selectivity. Altogether, the results highlight the potential of trehalose-polyamine/pDNA nanocomplex monoformulations to achieve targeting transfection without the need for any additional cell- or organ-sorting component.

Multifunctional Poly(2-ethyl-2-oxazoline) Copolymers Containing Dithiolane and Pentafluorophenyl Esters as Effective Reactive Linkers for Gold Surface Coatings.

Surface functionalization with biological macromolecules is an important task for the development of sensor materials, whereby the interaction with other biological materials should be suppressed. In this work, we developed a novel multifunctional poly(2-ethyl-2-oxazoline)-dithiolane conjugate as a versatile linker for gold surface immobilization of amine-containing biomolecules, containing poly(2-ethyl-2-oxazoline) as antifouling polymer, dithiolane for surface immobilization, and activated esters for protein conjugation. First, a well-defined carboxylic acid containing copoly(2-ethyl-2-oxazoline) was synthesized by cationic ring-opening copolymerization of 2-ethyl-2-oxazoline with a methyl ester-containing 2-oxazoline monomer, followed by postpolymerization modifications. The side-chain carboxylic groups were then converted to amine-reactive pentafluorophenyl (PFP) ester groups. Part of the PFP groups was used for the attachment of the dithiolane moiety, which can efficiently bind to gold surfaces. The final copolymer contained 1.4 mol% of dithiolane groups and 4.5 mol% of PFP groups. The copolymer structure was confirmed by several analytical techniques, including NMR spectroscopy and size-exclusion chromatography. The kinetics of the PFP ester aminolysis and hydrolysis demonstrated significantly faster amidation compared to hydrolysis, which is essential for subsequent protein conjugation. Successful coating of gold surfaces with the polymer was confirmed by spectroscopic ellipsometry, showing a polymer brush thickness of 4.77 nm. Subsequent modification of the coated surfaces was achieved using bovine serum albumin as a model protein. This study introduces a novel reactive polymer linker for gold surface functionalization and offers a versatile polymer platform for various applications including biosensing and surface functionalization.

Antimicrobial Properties of New Polyamines Conjugated with Oxygen-Containing Aromatic Functional Groups.

Antibiotic resistance is now a first-order health problem, which makes the development of new families of antimicrobials imperative. These compounds should ideally be inexpensive, readily available, highly active, and non-toxic. Here, we present the results of our investigation regarding the antimicrobial activity of a series of natural and synthetic polyamines with different architectures (linear, tripodal, and macrocyclic) and their derivatives with the oxygen-containing aromatic functional groups 1,3-benzodioxol, ortho/para phenol, or 2,3-dihydrobenzofuran. The new compounds were prepared through an inexpensive process, and their activity was tested against selected strains of yeast, as well as Gram-positive and Gram-negative bacteria. In all cases, the conjugated derivatives showed antimicrobial activity higher than the unsubstituted polyamines. Several factors, such as the overall charge at physiological pH, lipophilicity, and the topology of the polyamine scaffold were relevant to their activity. The nature of the lipophilic moiety was also a determinant of human cell toxicity. The lead compounds were found to be bactericidal and fungistatic, and they were synergic with the commercial antifungals fluconazole, cycloheximide, and amphotericin B against the yeast strains tested.

Unprecedented reactivity of polyamines with aldehydic DNA modifications: structural determinants of reactivity, characterization and enzymatic stability of adducts.

Apurinic/apyrimidinic (AP) sites, 5-formyluracil (fU) and 5-formylcytosine (fC) are abundant DNA modifications that share aldehyde-type reactivity. Here, we demonstrate that polyamines featuring at least one secondary 1,2-diamine fragment in combination with aromatic units form covalent DNA adducts upon reaction with AP sites (with concomitant cleavage of the AP strand), fU and, to a lesser extent, fC residues. Using small-molecule mimics of AP site and fU, we show that reaction of secondary 1,2-diamines with AP sites leads to the formation of unprecedented 3'-tetrahydrofuro[2,3,4-ef]-1,4-diazepane ('ribodiazepane') scaffold, whereas the reaction with fU produces cationic 2,3-dihydro-1,4-diazepinium adducts via uracil ring opening. The reactivity of polyamines towards AP sites versus fU and fC can be tuned by modulating their chemical structure and pH of the reaction medium, enabling up to 20-fold chemoselectivity for AP sites with respect to fU and fC. This reaction is efficient in near-physiological conditions at low-micromolar concentration of polyamines and tolerant to the presence of a large excess of unmodified DNA. Remarkably, 3'-ribodiazepane adducts are chemically stable and resistant to the action of apurinic/apyrimidinic endonuclease 1 (APE1) and tyrosyl-DNA phosphoesterase 1 (TDP1), two DNA repair enzymes known to cleanse a variety of 3' end-blocking DNA lesions.

Pyrene-Containing Polyamines as Fluorescent Receptors for Recognition of PFOA in Aqueous Media.

The globally widespread perfluorooctanoic acid (PFOA) is a concerning environmental contaminant, with a possible toxic long-term effects on the environment and human health The development of sensible, rapid, and low-cost detection systems is a current change in modern environmental chemistry. In this context, two triamine-based chemosensors, L1 and L2, containing a fluorescent pyrene unit, and their Zn(II) complexes are proposed as fluorescent probes for the detection of PFOA in aqueous media. Binding studies carried out by means of fluorescence and NMR titrations highlight that protonated forms of the receptors can interact with the carboxylate group of PFOA, thanks to salt bridge formation with the ammonium groups of the aliphatic chain. This interaction induces a decrease in the fluorescence emission of pyrene at neutral and slightly acidic pH values. Similarly, emission quenching has also been observed upon coordination of PFOA by the Zn(II) complexes of the receptors. These results evidence that simple polyamine-based molecular receptors can be employed for the optical recognition of harmful pollutant molecules, such as PFOA, in aqueous media.

Enhanced alpha-amylase inhibition activity of amine-terminated PAMAM dendrimer stabilized pure copper-doped magnesium oxide nanoparticles.

The present work aims to prepare copper-doped MgO nanoparticles via a sol-gel approach and study their antidiabetic alpha-amylase inhibition activity with undoped MgO nanoparticles. The ability of G5 amine-terminated polyamidoamine (PAMAM) dendrimer for the controlled release of copper-doped MgO nanoparticles to exhibit alpha-amylase inhibition activity was also evaluated. The synthesis of MgO nanoparticles via sol-gel approach and optimization of calcination temperature and time has led to the formation of nanoparticles with different shapes (spherical, hexagonal, and rod-shaped) and a polydispersity in size ranging from 10 to 100 nm with periclase crystalline phase. The presence of copper ions in the MgO nanoparticles has altered their crystallite size, eventually modifying their size, morphology, and surface charge. The efficiency of dendrimer to stabilize spherical copper-doped MgO nanoparticles (ca. 30 %) is higher than in other samples, which was confirmed by UV-Visible, DLS, FTIR, and TEM analysis. The amylase inhibition assay emphasized that the dendrimer nanoparticles stabilization has led to the prolonged enzyme inhibition ability of MgO and copper-doped MgO nanoparticles for up to 24 h.

Structural basis of amine odorant perception by a mammal olfactory receptor.

Odorants are detected as smell in the nasal epithelium of mammals by two G-protein-coupled receptor families, the odorant receptors and the trace amine-associated receptors1,2 (TAARs). TAARs emerged following the divergence of jawed and jawless fish, and comprise a large monophyletic family of receptors that recognize volatile amine odorants to elicit both intraspecific and interspecific innate behaviours such as attraction and aversion3-5. Here we report cryo-electron microscopy structures of mouse TAAR9 (mTAAR9) and mTAAR9-Gs or mTAAR9-Golf trimers in complex with ß-phenylethylamine, N,N-dimethylcyclohexylamine or spermidine. The mTAAR9 structures contain a deep and tight ligand-binding pocket decorated with a conserved D3.32W6.48Y7.43 motif, which is essential for amine odorant recognition. In the mTAAR9 structure, a unique disulfide bond connecting the N terminus to ECL2 is required for agonist-induced receptor activation. We identify key structural motifs of TAAR family members for detecting monoamines and polyamines and the shared sequence of different TAAR members that are responsible for recognition of the same odour chemical. We elucidate the molecular basis of mTAAR9 coupling to Gs and Golf by structural characterization and mutational analysis. Collectively, our results provide a structural basis for odorant detection, receptor activation and Golf coupling of an amine olfactory receptor.

PAMAM-Functionalized Paper as a New Substrate for the Paper Spray Mass Spectrometry Measurement of Proteins.

Paper surface functionalization with polyamidoamine (PAMAM) dendrimers has been developed for increased sensitivity analysis of proteins by paper spray mass spectrometry (PS-MS). PAMAM is a branched polymeric compound with an ethylenediamine core linked to repeating PAMAM units that generates an outer surface rich in primary amines. These positively charged amine groups can interact electrostatically with negatively charged residues (e.g., aspartate, glutamate) on the protein surface. PAMAM inner amide moieties can also promote hydrogen bonding with protein surface oxygens, making PAMAM a useful material for protein extraction. PAMAM-functionalized PS-MS paper strips were used to extract proteins from biofluids, dipped in acetonitrile to remove unbound constituents, dried, and then measured with PS-MS. The use of this strategy was optimized and compared with unmodified paper strips. PAMAM-functionalized paper substrates provided sixfold greater sensitivity for albumin, 11-fold for hemoglobin, sevenfold for insulin, and twofold for lysozyme. The analytical performance of the functionalized paper substrate was evaluated through the analysis of albumin in urine, achieving linearity with R2 > 0.99, LOD of 1.1 µg mL-1, LOQ of 3.8 µg mL-1, precision better than 10%, and relative recovery 70-83%. The method was applied to quantify urinary albumin from nine anonymous patient samples (concentrations ranged from 6.5 to 77.4 µg mL-1), illustrating its potential for the diagnosis of microalbuminuria. These data demonstrate the utility of paper modification with the PAMAM dendrimer for sensitive PS-MS analysis of proteins, opening a path for further applications in clinical diagnosis through the analysis of disease-related proteins.

Determination of polyamines in urine via electrospun nanofibers-based solid-phase extraction coupled with GC-MS and application to gastric cancer patients.

The simultaneous determination of polyamines and their metabolites in urine samples was achieved by gas chromatography-mass spectrometry in the selected ion monitoring mode. After conjugating with the ion-pair reagent bis-2-ethylhexylphosphate in the aqueous phase, the polyamines in the samples were extracted with polystyrene nanofiber-based packed-fiber solid-phase extraction followed by a derivatization step using pentafluoropropionyl anhydride. With optimal conditions, all analytes were separated well. For analytes of putrescine, cadaverine, N-acetylputrescine, and N-acetylcadaverine, the linearity was good in the range of 0.05-500 µmol/L (R2  ≥ 0.993). While for spermidine, spermine, acetylspermidine, N8 -acetylspermidine, and N-acetylspermine, the linearity was good in the range of 0.5-500 µmol/L (R2  ≥ 0.990). The recoveries of three spiked concentrations (0.5, 5, 300 µmol/L) were 85.6%-108.4%, and relative standard deviations for intra- and interday were in the range of 2.9%-13.4% and 4.5%-15.1%, respectively. The method was successfully applied to the analysis of urine samples of gastric cancer patients. The results showed that the levels of most polyamines and N-acetylated polyamines from the patient group were significantly higher than those from the control group. The altered concentrations of the above-mentioned metabolites suggest their role in the pathogenesis of gastric cancer, and they should be further evaluated as potential markers of gastric cancer.

A combined ligand and target-based virtual screening strategy to repurpose drugs as putrescine uptake inhibitors with trypanocidal activity.

Chagas disease, also known as American trypanosomiasis, is a neglected tropical disease caused by the protozoa Trypanosoma cruzi, affecting nearly 7 million people only in the Americas. Polyamines are essential compounds for parasite growth, survival, and differentiation. However, because trypanosomatids are auxotrophic for polyamines, they must be obtained from the host by specific transporters. In this investigation, an ensemble of QSAR classifiers able to identify polyamine analogs with trypanocidal activity was developed. Then, a multi-template homology model of the dimeric polyamine transporter of T. cruzi, TcPAT12, was created with Rosetta, and then refined by enhanced sampling molecular dynamics simulations. Using representative snapshots extracted from the trajectory, a docking model able to discriminate between active and inactive compounds was developed and validated. Both models were applied in a parallel virtual screening campaign to repurpose known drugs as anti-trypanosomal compounds inhibiting polyamine transport in T. cruzi. Montelukast, Quinestrol, Danazol, and Dutasteride were selected for in vitro testing, and all of them inhibited putrescine uptake in biochemical assays, confirming the predictive ability of the computational models. Furthermore, all the confirmed hits proved to inhibit epimastigote proliferation, and Quinestrol and Danazol were able to inhibit, in the low micromolar range, the viability of trypomastigotes and the intracellular growth of amastigotes.

Toughening Polyamidoamine Hydrogels through Covalent Grafting of Short Silk Fibers.

Linear amphoteric polyamidoamines (PAAs) are usually water-soluble, biodegradable and biocompatible. Crosslinked PAAs form in water hydrogels, retaining most of the favorable properties of their linear counterparts. The hydrogels prepared by the radical post-polymerization of the oligo-α,ω-bisacrylamido-terminated PAA called AGMA1, obtained by the polyaddition of 4-aminobutylguanidine (agmatine) with 2,2-bis(acrylamido)acetic acid, exhibit excellent cell-adhesion properties both in vitro and in vivo. However, due to their low mechanical strength, AGMA1 hydrogels cannot be sewn to biological tissues and need to be reinforced with fibrous materials. In this work, short silk fibers gave excellent results in this sense, proving capable of establishing covalent bonds with the PAA matrix, thanks to their lysine content, which provided amino groups capable of reacting with the terminal acrylamide groups of the AGMA1 precursor in the final crosslinking phase. Morphological analyses demonstrated that the AGMA1 matrix was intimately interconnected and adherent to the silk fibers, with neither visible holes nor empty volumes. The silk/H-AGMA1 composites were still reversibly swellable in water. In the swollen state, they could be sewn and showed no detachment between fibers and matrix and exhibited significantly improved mechanical properties compared with the plain hydrogels, particularly as regards their Young's modulus and elongation at break.

pH- and Functionalization-Dependent Host-Guest Interactions Between Fluorescein and Various Poly(amidoamine) Dendrimers.

Dendrimers are branched macromolecules that can be functionalized with a large variety of chemical moieties. Dendrimers can therefore be specifically designed to interact with target molecules. Although tailored dendrimers hold promise for targeted drug delivery and wastewater cleanup, these applications require more detailed and systematic studies on how dendrimer-guest interactions depend on environmental conditions. In light of this need, we studied pH-dependent interactions between fluorescein and poly(amidoamine) dendrimers with three different terminal groups. Crucially, both fluorescein and dendrimers have multiple protonation equilibria, which can enable interactions in different pH windows through various possible mechanisms. Such interactions are studied through UV-vis and fluorescence spectroscopies, which reveal a redshift that occurs upon fluorescein-dendrimer binding. The resulting pH-dependent spectra are complex but can be analyzed quantitatively with an open-source mathematical protocol. Consequently, we show that fluorescein binds across four pH units with amine-terminated dendrimers, across two units with hydroxyl-terminated dendrimers and does not interact attractively with carboxyl-terminated dendrimers. These functionalization-dependent host-guest interactions stabilize fluorescein's dianionic form and are predominantly electrostatically driven, with likely auxiliary hydrogen and CH-π bonding. Notably, these auxiliary mechanisms appear too weak to drive dendrimer-fluorescein interactions on their own. Overall, this work yields valuable insights into dendrimer-fluorescein association and provides a readily reproducible framework for studying host-guest interactions.

Interactions of Functionalized PAMAM Dendrimers with Model Cell Membranes Studied via Spin-Labeling Technique.

Polyamidoamine (PAMAM) dendrimers are exploited as drug carriers in various biomedical research fields, especially cancer therapy. The present study analyzes the interactions occurring between differently functionalized PAMAM dendrimers, namely, amine, acetamide, and 3-methoxy-carbonyl-5-pyrrolidonyl ("pyrrolidone"), and model membranes, namely, sodium dodecyl sulfate (SDS), sodium hexadecylsulfate (SHS) micelles, and egg-lecithin liposomes. For this purpose, the dendrimers were spin-labeled with the 3-carbamoyl-PROXYL radical. 1H-NMR spectra allowed the verification not only that labeling was successful but also that acetamide and (even more so) pyrrolidone functions shield the proton signals from the influence of the neighboring nitroxide groups. The computer-aided analysis of the electron paramagnetic resonance (EPR) spectra showed that the dendrimers with the acetamide function largely (60%) entered the SDS-micelles interface, while the amino-dendrimer electrostatically interacted with both the SDS and SHS surface forming dendrimer aggregates in solution. The pyrrolidone-dendrimers showed an intermediate behavior between those with the amino and acetamide functions. The acetamide- and pyrrolidone-dendrimers weakly interacted with the lecithin liposome surface, with a synergy between hydrophilic and hydrophobic interactions. Conversely, liposomes/amino-dendrimers interactions were quite strong and led to dendrimer aggregation at the liposome surface in solution. This information showed that acetamide- and pyrrolidone-dendrimers may be used as good alternatives to amino-dendrimers for drug delivery.

Synthesis of Novel Lipophilic Polyamines via Ugi Reaction and Evaluation of Their Anticancer Activity.

Natural polyamines (PAs) are involved in the processes of proliferation and differentiation of cancer cells. Lipophilic synthetic polyamines (LPAs) induce the cell death of various cancer cell lines. In the current paper, we have demonstrated a new method for synthesis of LPAs via the multicomponent Ugi reaction and subsequent reduction of amide groups by PhSiH3. The anticancer activity of the obtained compounds was evaluated in the A-549, MCF7, and HCT116 cancer cell lines. For the first time, it was shown that the anticancer activity of LPAs with piperazine fragments is comparable with that of aliphatic LPAs. The presence of a diglyceride fragment in the structure of LPAs appears to be a key factor for the manifestation of high anticancer activity. The findings of the study strongly support further research in the field of LPAs and their derivatives.

Practical Synthesis of Polyamine Succinamides and Branched Polyamines.

Antibiotic resistance is now a growing threat to human health, further exacerbated by the lack of new antibiotics. We describe the practical synthesis of a series of substituted polyamine succinamides and branched polyamines that are potential new antibiotics against both Gram-positive and Gram-negative bacteria, including MRSA and Pseudomonas aeruginosa. They are prepared via 1,4-Michael addition of acrylonitrile and then hydrogenation of the nitrile functional groups to primary amines. They are built upon the framework of the naturally occurring polyamines thermine (3.3.3, norspermine) and spermine (3.4.3), homo- and heterodimeric polyamine succinic amides. Linking two of the same or different polyamines together via amide bonds can be achieved by introducing a carboxylic acid group on the first polyamine, then coupling that released carboxylic acid to a free primary amine in the second polyamine. If the addition of positive charges on the amino groups along the polyamine chains are a key factor in their antimicrobial activity against Gram-negative bacteria, then increasing them will increase the antimicrobial activity. Synthesising polyamine amide dimers will increase the total net positive charge compared to their monomers. The design and practical synthesis of such homo- and hetero-dimers of linear polyamines, spermine and norspermine, are reported. Several of these compounds do not display significant antibacterial activity against Gram-positive or Gram-negative bacteria, including MRSA and Pseudomonas aeruginosa. However, the most charged analogue, a branched polyamine carrying eight positive charges at physiological pH, displays antibiofilm activity with a 50 % reduction in PAO1 at 16-32 µg mL-1 .

Fluorescent melamine-formaldehyde/polyamine coatings for microcapsules enabling their tracking in composites.

This study aimed the development of fluorescent melamine-formaldehyde (MF)/polyamine coatings for labelling of prefabricated microcapsules and their tracking in composites. The composition of the fluorescent MF coatings was studied by FTIR spectroscopy, thermogravimetric analysis, and elemental analysis. The characteristics of the coatings and its deposition on different surfaces were investigated using optical and fluorescence microscopy and fluorescence spectroscopy. MF prepolymers were polymerised with tri- and polyamines yielding in fluorescent coatings without addition of fluorescent dyes. Both, MF/poly(ethylene imine) and MF/poly(vinyl amine) (PVAm) coated glass beads showed maximum fluorescence at an excitation wavelength of λmax = 360 nm with the emission maxima at λmax = 490 nm and λmax = 410 nm, correspondingly. The MF/PVAm polymer was coated on diuron-poly(methyl methacrylate) microcapsules and tracked in highly filled composites (water-based plaster/paint) to show its applicability. MF/polyamine coatings were identified as promising materials for the fluorescent labelling of prefabricated microcapsules.