Aromatic systems with two and three pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile fragments as electron-transporting organic semiconductors exhibiting long-lived emissions.

The pyridine-3,5-dicarbonitrile moiety has gained significant attention in the field of materials chemistry, particularly in the development of heavy-metal-free pure organic light-emitting diodes (OLEDs). Extensive research on organic compounds exhibiting thermally activated delayed fluorescence (TADF) has led to numerous patents and research articles. This study focuses on the synthesis and investigation of the semiconducting properties of polyaromatic π-systems containing two and three fragments of pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile.

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.

The Specificity and Broad Multitarget Properties of Ligands for the Free Fatty Acid Receptors FFA3/GPR41 and FFA2/GPR43 and the Related Hydroxycarboxylic Acid Receptor HCA2/GPR109A.

The paradigm of ligand-receptor interactions postulated as "one compound-one target" has been evolving; a multi-target, pleiotropic approach is now considered to be realistic. Novel series of 1,4,5,6,7,8-hexahydro-5-oxoquinolines, pyranopyrimidines and S-alkyl derivatives of pyranopyrimidines have been synthesized in order to characterise their pleiotropic, multitarget activity on the FFA3/GPR41, FFA2/GPR43, and HCA2/GPR109A receptors. Hexahydroquinoline derivatives have been known to exhibit characteristic activity as FFA3/GPR41 ligands, but during this study we observed their impact on FFA2/GPR43 and HCA2/GPR109A receptors as well as their electron-donating activity.

Screening of SIRT6 inhibitors and activators: A novel activator has an impact on breast cancer cells.

Sirtuin 6 (SIRT6), a member of sirtuin family (SIRT1-7), regulates a variety of cellular processes involved in aging, metabolism, and cancer. Dysregulation of SIRT6 is widely observed in different breast cancer subtypes; however, the role and function of SIRT6 in cancer development remain largely unexplored. The aim of this study was to identify novel compounds targeting SIRT6 which may provide a new approach in development of anti-cancer therapy for breast cancer.

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.

Antifungal activity of styrylpyridinium compounds against Candida albicans.

We synthesized a set of 13 new and earlier described styrylpyridinium compounds (N-alkyl styrylpyridinium salts with bromide or tosylate anions) in order to evaluate antifungal activity against C. albicans cells, to assay the possible synergism with fluconazole, and to estimate cytotoxicity to mammalian cells. All compounds were synthesized according to a well-known two-step procedure involving alkylation of γ-picoline with appropriate alkyl bromide and further condensation with substituted benzaldehyde.

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.

Screening Pyridine Derivatives against Human Hydrogen Sulfide-synthesizing Enzymes by Orthogonal Methods.

Biosynthesis of hydrogen sulfide (HS), a key signalling molecule in human (patho)physiology, is mostly accomplished by the human enzymes cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (MST). Several lines of evidence have shown a close correlation between increased HS production and human diseases, such as several cancer types and amyotrophic lateral sclerosis. Identifying compounds selectively and potently inhibiting the human HS-synthesizing enzymes may therefore prove beneficial for pharmacological applications.

Synthesis of Linear and V-Shaped Carbazolyl-Substituted Pyridine-3,5-dicarbonitriles Exhibiting Efficient Bipolar Charge Transport and E-Type Fluorescence.

With the aim of developing all-organic bipolar semiconductors with high charge mobility and efficient E-type fluorescence (so-called TADF) as environmentally friendly light-emitting materials for optoelectronic applications, four noble metals-free dyes with linear and V-shapes were designed using accepting pyridine-3,5-dicarbonitrile and donating carbazole units. By exploiting a donor-acceptor design strategy and using moieties with different donating and accepting abilities, TADF emitters with a wide variety of molecular weights were synthesized to achieve the optimum combination of charge-transporting and fluorescent properties in one TADF molecule. Depending on molecule structures, different TADF emitters capable of emitting in the range from 453 to 550 nm with photoluminescence quantum yields up to 98 % for the solutions in oxygen-free toluene were obtained.

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.

Modifications of expression of genes and proteins involved in DNA repair and nitric oxide metabolism by carbatonides [disodium-2,6-dimethyl-1,4-dihydropyridine- 3,5-bis(carbonyloxyacetate) derivatives] in intact and diabetic rats.

Studies on the pathogenesis of diabetes mellitus complications indicate that the compounds reducing free radicals and enhancing DNA repair could be prospective as possible remedies. Carbatonides, the disodium-2,6-dimethyl-1,4- dihydropyridine-3,5-bis(carbonyloxyacetate) derivatives, were tested for these properties. EPR spectroscopy showed that metcarbatone was an effective scavenger of hydroxyl radicals produced in the Fenton reaction, etcarbatone, and propcarbatone were less effective, styrylcarbatone was ineffective.

Dihydropyridine Derivatives as Cell Growth Modulators In Vitro.

The effects of eleven 1,4-dihydropyridine derivatives (DHPs) used alone or together with prooxidant anticancer drug doxorubicin were examined on two cancer (HOS, HeLa) and two nonmalignant cell lines (HMEC, L929). Their effects on the cell growth (H-thymidine incorporation) were compared with their antiradical activities (DPPH assay), using well-known DHP antioxidant diludine as a reference. Thus, tested DHPs belong to three groups: (1) antioxidant diludine; (2) derivatives with pyridinium moieties at position 4 of the 1,4-DHP ring; (3) DHPs containing cationic methylene onium (pyridinium, trialkylammonium) moieties at positions 2 and 6 of the 1,4-DHP ring.

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.

Design, synthesis and 3D-QSAR studies of novel 1,4-dihydropyridines as TGFβ/Smad inhibitors.

Targeting TGFβ/Smad signaling is an attractive strategy for several therapeutic applications given its role as a key player in many pathologies, including cancer, autoimmune diseases and fibrosis. The class of b-annelated 1,4-dihydropyridines (DHPs) represents promising novel pharmacological tools as they interfere with this pathway in a novel fashion, i.e.

Crystal structure of 3-amino-5,5-dimethyl-2-[(E)-2-nitro-ethen-yl]cyclo-hex-2-en-1-one.

The asymmetric unit of the title compound, C10H14N2O3, contains two independent mol-ecules with similar conformations. In the both mol-ecules, the cyclo-hexene rings adopt the same envelope conformation with the flap C atoms lying 0.658 (3) and 0.

3-Acetyl-2-methyl-4-(pyridin-3-yl)-1,4-di-hydro-indeno-[1,2-b]pyridin-5-one.

In the title compound, C20H16N2O2, the condensed tricyclic fragment is near to planar, with an r.m.s.

3-{3,5-Bis[(2-but-oxy-eth-oxy)carbon-yl]-2,6-dimethyl-1,4-dihydro-pyridin-4-yl}-1-[(3,4,5-trimeth-oxy-benzo-yl)meth-yl]pyridinium bromide.

In the title salt, C37H51N2O10(+)·Br(-), the 1,4-dihydro-pyridine (1,4-DHP) ring adopts a slighly puckered boat conformation. The N and opposite C atoms deviate from the least-squares plane calculated through the four other ring atoms by 0.068 (5) and 0.

Methyl 6-oxo-4-phenyl-2-[(Z)-2-(pyridin-2-yl)ethen-yl]-1,4,5,6-tetra-hydro-pyridine-3-carboxyl-ate.

In the title mol-ecule, C20H18N2O3, an intra-molecular N-H⋯O hydrogen bond leads to a cis conformation of the pyridinyl-vinyl fragment. The phenyl and pyridine rings are inclined to one another by 77.3 (1) °.

Intramolecular C-H···O hydrogen bonding in 1,4-dihydropyridine derivatives.

The diastereotopy of the methylene protons at positions 2 and 6 in 1,4-dihydropiridine derivatives with various substituents has been investigated. NMR spectroscopy and quantum chemistry calculations show that the CH···O intramolecular hydrogen bond is one of the factors amplifying the chemical shift differences in the 1H-NMR spectra.

Effect of 4-aryl-2-methyl-5-nitro-1,4-dihydropyridine-3-carboxylates on the guinea pig papillary muscle and isolated human vena saphena magna that is used for coronary artery bypass grafting.

Background: The goal of this study was to estimate: (i) the action of 5-nitro-substituted 1,4-dihydropyridines as well as Bay K 8644 (CAS [71145-03-4]) and CGP 28392 (CAS [89289-93-0]) on cardiac action potential duration (APD) and isometric contraction in the isolated guinea pig papillary muscles; (ii) whether the effects of 2-propoxyethyl 4-(2-difluoromethoxyphe-nyl)-2-methyl-5-nitro-1,4-dihydropyridine-3-carboxylate on the lengthening of cardiac APD were related to certain potassium channels (e.g., I(K1), K(ATP) and I(K)); and (iii) the modulation of the contraction-relaxation effects on isolated human vena saphena magna samples using three 5-nitro-substituted 1,4-dihydropyridine derivatives, displaying the positive inotropic and AP duration effects.

Growth modulation of human cells in vitro by mild oxidative stress and 1,4-dihydropyridine derivative antioxidants.

Reactive oxygen species and lipid peroxidation products are not only cytotoxic but may also modulate signal transduction in cells. Accordingly, antioxidants may be considered as modifiers of cellular redox signaling. Therefore, the effects of two novel synthetic antioxidants, analogues of 1,4-dihydropyridine derivatives, cerebrocrast and Z41-74 were analysed in vitro on human osteosarcoma cell line HOS, the growth of which can be modulated by lipid peroxidation.

Effect of cerebrocrast on body and organ weights, food and water intake, and urine output of normal rats.

Type 2 diabetes is associated with obesity, insulin resistance, hyperglycemia, hyperphagia, polyuria, body weight gain, excessive secretion of glucocorticoids (GCs), thymus involution, adrenal gland hypertrophy, diabetic nephropathy, etc. We examined the effect of cerebrocrast, a new antidiabetic agent (synthesized in the Latvian Institute of Organic Synthesis), on body weight, food and water intake, urine output, and on changes of organ weight: that is, kidney, thymus, adrenal gland of normal rats. Cerebrocrast was administered at doses of 0.

Acute effect of antidiabetic 1,4-dihydropyridine compound cerebrocrast on cardiac function and glucose metabolism in the isolated, perfused normal rat heart.

Diabetes mellitus (DM) is an important cardiovascular risk factor and is associated with abnormalities in endothelial and vascular smooth muscle cell function, evoked by chronic hyperglycemia and hyperlipidemia. Chronic insulin deficiency or resistance is marked by decreases in the intensity of glucose transport, glucose phosphorylation, and glucose oxidation, plus decreases in ATP levels in cardiac myocytes. It is important to search for new agents that promote glucose consumption in the heart and partially inhibit extensive fatty acid beta-oxidation observed in diabetic, ischemia.