Search Results (7)

A new method for the synthesis of azido-propargyloxy derivatives of 1,3,5-triazine has been developed utilizing the nitrosation of hydrazyno-1,3,5-triazines. New hydrazines (2-hydrazino-4,6-bis(propargyloxy)-1,3,5-triazine and 2,4-dihydrazino-6-propargyloxy-1,3,5-triazine) were synthesized and characterized via FTIR, NMR spectroscopy and elemental analysis. The hyperbranched polymers with azide (diazide monomer) and propargyloxy terminal groups were obtained via the azide-alkyne polycycloaddition reaction of diazide and monoazide AB₂-type monomers. The antibacterial activity against Escherichia coli bacteria of 2,4,6-trispropargyloxy-1,3,5-triazine, 2-azido-4,6-bispropargyloxy-1,3,5-triazine, and 2,4-diazido-6-propargyloxy-1,3,5-triazine and their hyperbranched polymers was studied. Only 2,4-diazido-6-propargyloxy-1,3,5-triazine has weak antibacterial activity in comparison with ampicillin. The cytotoxicity of these compounds against M-HeLa, FetMSC, and Vero cell lines was also studied. 2,4,6-trispropargyloxy-1,3,5-triazine does not show any cytotoxic effect (IC₅₀ ≥ 280 µM). It was shown that the presence of an azide group in the compound directly affects the cytotoxic effect. Hyperbranched polymers have a less cytotoxic effect against M-HeLa (IC₅₀ > 100) in comparison with monomers (IC₅₀ = 90–99 µM). This makes it possible to use these polymers as the basis for biocompatible materials in biomedical applications. Full article

The development of novel biologically active nanopharmaceuticals is a topical problem of medicine. Water-soluble fullerene derivatives are of particular interest due to their ability to regulate intracellular metabolism of reactive oxygen species (ROS) by direct oxidation or effects on oxidative and signaling enzymes. Here, we studied the effect of a water-soluble chlorine-containing derivative of C₆₀ fullerene on human embryonic lung fibroblasts. MTT tests, intracellular ROS visualization, detection of the ROS-associated gene and protein expression, repair, cell proliferation and cell cycle regulation, and quantitation of oxidative DNA damage were used. Within the first three hours after exposure, antioxidant effects were revealed. Later, oxidative damage appeared. Thus, the studied compound had an ambiguous effect on ROS metabolism associated with a switch in the regulatory effect, which must be taken into account when assessing its biological activity and toxicity. Full article

Cross-coupling reactions have changed the way complex molecules are synthesized. In particular, Suzuki–Miyaura and Buchwald–Hartwig amination reactions have given opportunities to elegantly make pharmaceutical ingredients. Indeed, these reactions are at the forefront of both the stages of drug development, medicinal chemistry, and process chemistry. On the one hand, these reactions have given medicinal chemists a resource to derivatize the core compound to arrive at scaffold rapidly. On the other hand, these cross couplings have offered the process chemists a smart tool to synthesize the development candidates safely, quickly, and efficiently. Generally, the application of cross-coupling reactions is broad. This review will specifically focus on their real (pharma) world applications in large-scale synthesis appearing in the last three years. Full article

Interleukin (IL)-15 and IL-17 are thought to play an important role in the pathogenesis of rheumatoid arthritis (RA) because both pro-inflammatory cytokines are found in synovial fluid of RA patients. In this study, we examined the pharmacological profiles of Y-320, a new phenylpyrazoleanilide immunomodulator. Y-320 inhibited IL-17 production by CD4 T cells stimulated with IL-15 with IC₅₀ values of 20 to 60 nM. Oral administration of Y-320 (0.3 to 3 mg/kg) significantly inhibited the development and progression of arthritis and joint destruction with reduction of IL-17 mRNA expression in arthritic joints of type II collagen-induced arthritis (CIA) in DBA/1J mice. Y-320 in combination with anti-murine tumor necrosis factor-α monoclonal antibody showed a synergistic effect on mouse CIA. Moreover, therapeutic treatment with Y-320 (0.3 and 1 mg/kg orally) ameliorated CIA in cynomolgus monkeys. Our results suggest that Y-320, an orally active inhibitor for IL-17 production, provides a useful therapy for RA. Full article

By studying the literature about tetracyclines (TCs), it becomes clearly evident that TCs are very dynamic molecules. In some cases, their structure-activity-relationship (SAR) are well known, especially against bacteria, while against other targets, they are virtually unknown. In other diverse fields of research—such as neurology, oncology and virology—the utility and activity of the tetracyclines are being discovered and are also emerging as new technological fronts. The first aim of this paper is to classify the compounds already used in therapy and prepare the schematic structure that includes the next generation of TCs. The second aim of this work is to introduce a new framework for the classification of old and new TCs, using a medicinal chemistry approach to the structure of those drugs. A fully documented Structure-Activity-Relationship (SAR) is presented with the analysis data of antibacterial and nonantibacterial (antifungal, antiviral and anticancer) tetracyclines. The lipophilicity and the conformational interchangeability of the functional groups are employed to develop the rules for TC biological activity. Full article

The biomaterials field is one of the largest and fastest growing research areas both in the scientific community and in the industrial one. Biomaterials are the result of collaborations between different disciplines: chemistry, medicine, pharmacology, engineering and biology. The objective of this collaboration is to lead to the implementation of new devices to restore form and human body functions. The research on biomaterials reflects the constant need to replace or supplement human tissues and organs that have been physiologically compromised due to disease or traumatic events. [...] Full article

The formation of complex systems is accompanied by the emergence of properties that are non-existent in the components. But what of the properties and behaviour of such components caught up in the formation of a system of a higher level of complexity? In this assay, we use a large variety of examples, from molecules to organisms and beyond, to show that systems merging into a complex system of higher order experience constraints with a partial loss of choice, options and independence. In other words, emergence in a complex system often implies reduction in the number of probable states of its components, a phenomenon we term dissolvence. This is seen in atoms when they merge to form molecules, in biomolecules when they form macromolecules such as proteins, and in macromolecules when they form aggregates such as molecular machines or membranes. At higher biological levels, dissolvence occurs for example in components of cells (e.g. organelles), tissues (cells), organs (tissues), organisms (organs) and societies (individuals). Far from being a destruction, dissolvence is understood here as a creative process in which information is generated to fuel the process of self-organisation of complex systems, allowing them to appear and evolve to higher states of organisation and emergence. Questions are raised about the relationship of dissolvence and adaptability; the interrelation with top-down causation; the reversibility of dissolvence; and the connection between dissolvence and anticipation. Full article