From Polymeric Nanoformulations to Polyphenols-Strategies for Enhancing the Efficacy and Drug Delivery of Gentamicin.

Gentamicin is an essential broad-spectrum aminoglycoside antibiotic that is used in over 40 clinical conditions and has shown activity against a wide range of nosocomial, biofilm-forming, multi-drug resistant bacteria. Nevertheless, the low cellular penetration and serious side effects of gentamicin, as well as the fear of the development of antibacterial resistance, has led to a search for ways to circumvent these obstacles. This review provides an overview of the chemical and pharmacological properties of gentamicin and offers six different strategies (the isolation of specific types of gentamicin, encapsulation in polymeric nanoparticles, hydrophobization of the gentamicin molecule, and combinations of gentamicin with other antibiotics, polyphenols, and natural products) that aim to enhance the drug delivery and antibacterial activity of gentamicin.

Development of Self-Assembling -1,4-Dihydropyridines: Detailed Studies of Bromination of Four Methyl Groups and Bromine Nucleophilic Substitution.

One of the most important steps in the synthesis of 1,4-dihydropyridine (1,4-DHP) amphiphiles is the bromination of methyl groups in positions 2 and 6 of the entire ring. However, up to now, only N-bromosuccinimide was mainly used for bromination 1,4-DHPs. In this work, the synthesis of -1,4-DHP derivatives with ethyl and dodecyl ester groups attached to 1,4-DHP ring at positions 3 and 5 was performed by Hantzsch synthesis.

Styrylpyridinium Derivatives for Fluorescent Cell Imaging.

A set of styrylpyridinium (SP) compounds was synthesised in order to study their spectroscopic and cell labelling properties. The compounds comprised different electron donating parts (julolidine, -dimethylaminophenyl, -methoxyphenyl, 3,4,5-trimethoxyphenyl), conjugated linkers (vinyl, divinyl), and an electron-withdrawing -alkylpyridinium part. Geminal or -compounds incorporating two styrylpyridinium (-SP) moieties at the 1,3-trimethylene unit were synthesised.

Synthesis and Characterization of Novel Amphiphilic -Benzyl 1,4-Dihydropyridine Derivatives-Evaluation of Lipid Monolayer and Self-Assembling Properties.

Liposomes and other nanoparticles have been widely studied as innovative nanomaterials because of their unique properties. Pyridinium salts, on the basis of 1,4-dihydropyridine (1,4-DHP) core, have gained significant attention due to their self-assembling properties and DNA delivery activity. This study aimed to synthesize and characterize original -benzyl substituted 1,4-dihydropyridines and evaluate the influence on structure modifications on compound physicochemical and self-assembling properties.

Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair.

The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage tissue ECM. In this study, we aimed to investigate the effect of mechanical load on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BM-MCSs) encapsulated into CS-tyramine-gelatin (CS-Tyr/Gel) hydrogel in order to evaluate the suitability of this composite for OA cartilage regeneration studies in vitro.

The Effects of Mechanical Load on Chondrogenic Responses of Bone Marrow Mesenchymal Stem Cells and Chondrocytes Encapsulated in Chondroitin Sulfate-Based Hydrogel.

Articular cartilage is vulnerable to mechanical overload and has limited ability to restore lesions, which leads to the development of chronic diseases such as osteoarthritis (OA). In this study, the chondrogenic responses of human bone marrow mesenchymal stem cells (BMMSCs) and OA cartilage-derived chondrocytes in 3D chondroitin sulfate-tyramine/gelatin (CS-Tyr)/Gel) hydrogels with or without experimental mechanical load have been investigated. Chondrocytes were smaller in size, had slower proliferation rate and higher level of intracellular calcium (iCa) compared to BMMSCs.

Design and Synthesis of Hepatitis B Virus (HBV) Capsid Assembly Modulators and Evaluation of Their Activity in Mammalian Cell Model.

Capsid assembly modulators (CAMs) have emerged as a promising class of antiviral agents. We studied the effects of twenty-one newly designed and synthesized CAMs including heteroaryldihydropyrimidine compounds (HAPs), their analogs and standard compounds on hepatitis B virus (HBV) capsid assembly. Cytoplasmic expression of the HBV core (HBc) gene driven by the exogenously delivered recombinant alphavirus RNA replicon was used for high level production of the full-length HBc protein in mammalian cells.

Data for characterisation of nanoformulations formed by cationic 1,4-dihydopyridine and calix[4]arene compositions.

In this data file the characterisation of nanoformulations obtained from calix[4]arene/1,4-dihydropyridine (1,4-DHP) compositions in the various component ratio in an aqueous medium was performed by dynamic light scattering (DLS) technique. The hydrodynamic diameters of nanoparticle main population, polydispersity index and stability of nanoformulation were determined. In this article provided data are directly related to the previously published research articles - "Gene delivery agents possessing antiradical activity: Self-assembling cationic amphiphilic 1,4-dihydropyridine derivatives" [1], and "Studies of the physicochemical and structural properties of self-assembling cationic pyridine derivatives as gene delivery agents" [2] where was described synthesis, transfection activity of 1,1'-((3,5-bis((dodecyloxy)carbonyl)-4-phenyl-1,4-dihydropyridine-2,6-diyl)bis(methylene))bis(pyridin-1-ium) dibromide presented in this data file; and with articles "Cationic amphiphilic calixarenes to compact DNA into small nanoparticles for gene delivery" [3] and "Self-aggregation in aqueous solution of amphiphilic cationic calix[4]arenes.

Mechanotransducive Biomimetic Systems for Chondrogenic Differentiation In Vitro.

Osteoarthritis (OA) is a long-term chronic joint disease characterized by the deterioration of bones and cartilage, which results in rubbing of bones which causes joint stiffness, pain, and restriction of movement. Tissue engineering strategies for repairing damaged and diseased cartilage tissue have been widely studied with various types of stem cells, chondrocytes, and extracellular matrices being on the lead of new discoveries. The application of natural or synthetic compound-based scaffolds for the improvement of chondrogenic differentiation efficiency and cartilage tissue engineering is of great interest in regenerative medicine.

Evaluation of Physicochemical Properties of Amphiphilic 1,4-Dihydropyridines and Preparation of Magnetoliposomes.

This study was focused on the estimation of the targeted modification of 1,4-DHP core with (1) different alkyl chain lengths at 3,5-ester moieties of 1,4-DHP (C, C and C); (2) N-substituent at position 1 of 1,4-DHP (N-H or N-CH); (3) substituents of pyridinium moieties at positions 2 and 6 of 1,4-DHP (H, 4-CN and 3-Ph); (4) substituent at position 4 of 1,4-DHP (phenyl and napthyl) on physicochemical properties of the entire molecules and on the characteristics of the obtained magnetoliposomes formed by them. It was shown that thermal behavior of the tested 1,4-DHP amphiphiles was related to the alkyl chains length, the elongation of which decreased their transition temperatures. The properties of 1,4-DHP amphiphile monolayers and their polar head areas were determined.

Pleiotropic Properties of Amphiphilic Dihydropyridines, Dihydropyridones, and Aminovinylcarbonyl Compounds.

Three groups of synthetic lipids are chosen for studies: (1) 1,4-dihydropyridines (1,4-DHPs) containing two cationic moieties and their analogues; (2) 3,4-dihydro-2(1)-pyridones containing a cationic moiety; and (3) acyclic, open-chain analogues, i.e., 2-amino-3-alkoxycarbonylalkylammonium derivatives.

Data for the cytotoxicity, self-assembling properties and synthesis of 4-pyridinium-1,4-dihydropyridines.

In this data file the synthetic procedures for preparation of the original 4-pyridinium-1,4-dihydropyridines (4-Py-1,4-DHP) and their parent compounds - dialkyl 2,6-dimethyl-4-(3-pyridyl)-1,4-dihydropyridine-3,5-dicarboxylates were described. In total, 5 unpublished compounds were obtained and characterised. All the structures of original compounds were confirmed by Nuclear Magnetic Resonance (NMR, including H NMR and C NMR) and low resolution mass spectra (MS) data.

Epigenetics in Breast Cancer Therapy-New Strategies and Future Nanomedicine Perspectives.

Epigenetic dysregulation has been recognized as a critical factor contributing to the development of resistance against standard chemotherapy and to breast cancer progression via epithelial-to-mesenchymal transition. Although the efficacy of the first-generation epigenetic drugs (epi-drugs) in solid tumor management has been disappointing, there is an increasing body of evidence showing that epigenome modulation, in synergy with other therapeutic approaches, could play an important role in cancer treatment, reversing acquired therapy resistance. However, the epigenetic therapy of solid malignancies is not straightforward.

Synthesis of Fluorinated 3,6-Dihydropyridines and 2-(Fluoromethyl)pyridines by Electrophilic Fluorination of 1,2-Dihydropyridines with Selectfluor.

New fluorinated 3,6-dihydropyridines were obtained by the electrophilic fluorination of 1,2-dihydropyridines with Selectfluor. These 3-fluoro-3,6-dihydropyridines were easily converted to corresponding pyridines by the elimination of hydrogen fluoride under mild conditions. A new approach to the synthesis of methyl 2-(fluoromethyl)-5-nitro-6-arylnicotinates by the fluorination of 3-fluoro-2-methyl-5-nitro-3,6-dihydropyridines or 1,2-dihydropyridines with Selectfluor has been developed.

Data for the synthesis and characterisation of 2,6-di(bromomethyl)-3,5-bis(alkoxycarbonyl)-4-aryl-1,4-dihydropyridines as important intermediates for synthesis of amphiphilic 1,4-dihydropyridines.

This data file describes the synthetic protocol for preparation of the original 2,6-di(bromomethyl)-3,5-bis(alkoxycarbonyl)-4-aryl-1,4-dihydropyridines. In total, 6 unpublished compounds were obtained and characterised. The 2,6-di(bromomethyl)-1,4-dihydropyridines are mainly used as intermediates for synthesis of various lipid-like compounds based on 1,4-dihydropyridine cycle.

Contribution of Molecular Structure to Self-Assembling and Biological Properties of Bifunctional Lipid-Like 4-(-Alkylpyridinium)-1,4-Dihydropyridines.

The design of nanoparticle delivery materials possessing biological activities is an attractive strategy for the development of various therapies. In this study, 11 cationic amphiphilic 4-(-alkylpyridinium)-1,4-dihydropyridine (1,4-DHP) derivatives differing in alkyl chain length and propargyl moiety/ties number and position were selected for the study of their self-assembling properties, evaluation of their cytotoxicity in vitro and toxicity on microorganisms, and the characterisation of their interaction with phospholipids. These lipid-like 1,4-DHPs have been earlier proposed as promising nanocarriers for DNA delivery.

Synthesis and Comparative Evaluation of Novel Cationic Amphiphile C12-Man-Q as an Efficient DNA Delivery Agent In Vitro.

New amphiphilic 1,4-DHP derivative with remoted cationic moieties at positions 2 and 6 was synthesised to study DNA delivery activity. The results were compared with data obtained for cationic 1,4-DHP derivative , which is known to be the most efficient one among the previously tested 1,4-DHP amphiphiles. We analysed the effects of concentration, complexation media, and complex/cell contact time on the gene delivery effectiveness and cell viability.

Direct Aminolysis of Ethoxycarbonylmethyl 1,4-Dihydropyridine-3-carboxylates.

The ethoxycarbonylmethyl esters of 1,4-dihydropyridines were directly converted into carbamoylmethyl esters in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) in good to excellent yields under mild conditions.

Studies of the physicochemical and structural properties of self-assembling cationic pyridine derivatives as gene delivery agents.

New amphiphilic pyridine derivatives containing dodecyloxycarbonyl substituents at positions 3 and 5 and cationic moieties at positions 2 and 6 have been designed and synthesised. Compounds of this type can be considered as synthetic lipids. The corresponding 1,4-dihydropyridine (1,4-DHP) derivatives have earlier been proposed as a promising tool for plasmid DNA (pDNA) delivery in vitro.

Base-Induced Rearrangement of Perhydronaphthalene-1,4-diol Monosulfonate Esters to 11-Oxatricyclo[5.3.1.0(2,6)]undecanes. Total Synthesis of Furanether B.

It is observed that mesylate 1 on exposure to Li(Ot-Bu)(3)AlH in refluxing toluene rearranges selectively to the 11-oxatricyclo[5.3.1.