Therapeutic Influence on Important Targets Associated with Chronic Inflammation and Oxidative Stress in Cancer Treatment

Chronic inflammation and oxidative stress are the interconnected pathological processes, which lead to cancer initiation and progression. The growing level of oxidative and inflammatory damage was shown to increase cancer severity and contribute to tumor spread. The overproduction of reactive oxygen species (ROS), which is associated with the reduced capacity of the endogenous cell defense mechanisms and/or metabolic imbalance, is the main contributor to oxidative stress. An abnormal level of ROS was defined as a predisposing factor for the cell transformation that could trigger pro-oncogenic signaling pathways, induce changes in gene expression, and facilitate accumulation of mutations, DNA damage, and genomic instability. Additionally, the activation of transcription factors caused by a prolonged oxidative stress, including NF-κB, p53, HIF1α, etc., leads to the expression of several genes responsible for inflammation. The resulting hyperactivation of inflammatory mediators, including TNFα, TGF-β, interleukins, and prostaglandins can contribute to the development of neoplasia. Pro-inflammatory cytokines were shown to trigger adaptive reactions and the acquisition of resistance by tumor cells to apoptosis, while promoting proliferation, invasion, and angiogenesis. Moreover, the chronic inflammatory response leads to the excessive production of free radicals, which further aggravate the initiated reactions. This review summarizes the recent data and progress in the discovery of mechanisms that associate oxidative stress and chronic inflammation with cancer onset and metastasis. In addition, the review provides insights for the development of therapeutic approaches and the discovery of natural substances that will be able to simultaneously inhibit several key oncological and inflammation-related targets

Management of innovation processes at the enterprises of the construction materials industry

The purpose of this paper is the development of a methodical approach to management of the parameters of the life cycle of innovations. This approach ensures the increase of the efficiency of economic activity by intensifying the processes of innovative development of industrial enterprises. As a result of the research, the features of the processes for implementing the life cycle of innovations were determined; the system of criteria for assessing the efficiency of management of the parameters of the life cycle of innovations was developed; a management model for the parameters of the life cycle of innovations was formed; and a management mechanism for the life cycle of innovations in a saturated market was developed

Formation of a portfolio of innovation projects based on management of their life cycle parameters

This paper presents the results of study of the analysis of the formation of a portfolio of innovation projects based on the management of their life cycle parameters. An algorithm for forming an innovation portfolio is proposed, which includes analysis of the duration of the life cycle stages and determining the level of competitiveness of the planned innovations in the portfolio, assessing risks, and forecasting the expected economic results when implementing them. An algorithm has been developed that allows choosing the optimal set of risk management methods as a part of an innovation project, which includes identifying factors that increase and decrease the impact of a particular risk on the innovation implementation process. The proposed methods of monitoring the competitiveness of innovation projects allow assessing the competitive possibilities of an innovation project, which allows determination of the main directions for its implementation

Thermo-cyclically operated metal oxide gas sensor arrays for analysis of dissolved volatile organic compounds in fermentation processes: Part I – Morphology aspects of the sensing behavior

For a comparative study of the gas sensing performance to dissolved volatile organic compounds (VOCs), the SnO2-powders have been prepared using two different fabrication routes; the flame-spray-pyrolysis (FSP) and the sol-gel (SG) route; and were admixed with the same additive-powders (alumina, YSZ, and NASICON). The morphology of the two different SnO2/additive families were investigated by ESEM analysis and Energy-dispersive X-Ray Spectroscopy (EDS). Both SnO2/additive material families were separately deposited as thick-film-layers on two four-fold sensor-chips which were simultaneously thermo-cyclically operated in a measurement cell combined with a carrier gas probe, which enables sensing tests with evaporated VOCs (acetic acid, propionic acid, ethanol, acetone) dissolved in water. The resulting Conductance-over-Time-Profiles (CTPs) highlight better sensitivities of most of the FSP-layers to all the analytes compared to the SG-prepared layers. Furthermore, the CTP shapes of the FSP layers show clearly enhanced specificity representing the individual analyte components. This was interpreted to be the consequence of the extremely fine, scarcely agglomerated grain morphology of FSP-prepared powders and their very narrow grain size distribution which provide better conditions for enhanced gas specific surface reactions. Results promise a better chemical analysis capability of dissolved VOCs by numerical analysis of the CTP of FSP-prepared gas sensitive layers

Management of innovation processes at the enterprises of the construction materials industry

The purpose of this paper is the development of a methodical approach to management of the parameters of the life cycle of innovations. This approach ensures the increase of the efficiency of economic activity by intensifying the processes of innovative development of industrial enterprises. As a result of the research, the features of the processes for implementing the life cycle of innovations were determined; the system of criteria for assessing the efficiency of management of the parameters of the life cycle of innovations was developed; a management model for the parameters of the life cycle of innovations was formed; and a management mechanism for the life cycle of innovations in a saturated market was developed

Novel Multitarget Hydroxamic Acids with a Natural Origin CAP Group against Alzheimer’s Disease: Synthesis, Docking and Biological Evaluation

Hydroxamic acids are one of the most promising and actively studied classes of chemical compounds in medicinal chemistry. In this study, we describe the directed synthesis and effects of HDAC6 inhibitors. Fragments of adamantane and natural terpenes camphane and fenchane, combined with linkers of various nature with an amide group, were used as the CAP groups. Accordingly, 11 original target compounds were developed, synthesized, and exposed to in vitro and in vivo biological evaluations, including in silico methods. In silico studies showed that all synthesized compounds were drug-like and could penetrate through the blood–brain barrier. According to the in vitro testing, hydroxamic acids 15 and 25, which effectively inhibited HDAC6 and exhibited anti-aggregation properties against β-amyloid peptides, were chosen as the most promising substances to study their neuroprotective activities in vivo. All in vivo studies were performed using 5xFAD transgenic mice simulating Alzheimer’s disease. In these animals, the Novel Object Recognition and Morris Water Maze Test showed that the formation of hippocampus-dependent long-term episodic and spatial memory was deteriorated. Hydroxamic acid 15 restored normal memory functions to the level observed in control wild-type animals. Notably, this effect was precisely associated with the ability to restore lost cognitive functions, but not with the effect on motor and exploratory activities or on the level of anxiety in animals. Conclusively, hydroxamic acid 15 containing an adamantane fragment linked by an amide bond to a hydrocarbon linker is a possible potential multitarget agent against Alzheimer’s disease

Design of Conjugates Based on Sesquiterpene Lactones with Polyalkoxybenzenes by “Click” Chemistry to Create Potential Anticancer Agents

Using the methodology of “click” chemistry, a singular method has been developed for the synthesis of unique conjugates based on sesquiterpene lactones: dehydrocostuslactone and alantolactone with polyalkoxybenzenes. To expand the structural range of the resulting conjugates, the length of the 1,2,3-triazole spacer was varied. For all synthesized compounds, the cytotoxic profile was determined on the cell lines of tumor origin (SH-SY5Y, HeLa, Hep-2, A549) and normal Hek 293 cells. It was found that the compounds based on alantolactone 7a–d with a long spacer and substances containing dehydrocostuslactone 10a–d with a short spacer have the greatest toxic effect. The decrease in cell survival under the action of these conjugates may be due to their ability to cause dissipation of the transmembrane potential of mitochondria and inhibit the process of glycolysis, leading to cell death. The obtained results confirm the assumption that the development of conjugates based on sesquiterpene lactones and polyalkoxybenzenes can be considered as a promising strategy for the search for potential antitumor agents

Water-Soluble Salts Based on Benzofuroxan Derivatives—Synthesis and Biological Activity

A series of novel water-soluble salts of benzofuroxans was achieved via aromatic nucleophilic substitution reaction of 4,6-dichloro-5-nitrobenzofuroxan with various amines. The salts obtained showed good effectiveness of the pre-sowing treatment of seeds of agricultural crops at concentrations of 20–40 mmol. In some cases, the seed treatment with salts leads not only to improved seed germination, but also to the suppression of microflora growth. Additionally, their anti-cancer activityin vitrohas been researched. The compounds with morpholine fragments or a fragment of N-dimethylpropylamine, demonstrated the highest cytotoxic activity, which is in good correlation with the ability to inhibit the glycolysis process in tumor cells. Two compounds 4e and 4g were selected for further experiments using laboratory animals. It was found that the lethal dose of 50% (LD50) is 22.0 ± 1.33 mg/kg for 4e and 13.75 ± 1.73 mg/kg for 4g, i.e., compound 4e is two times less toxic than 4g, according to the mouse model in vivo. It was shown that the studied compounds exhibit antileukemia activity after a single intraperitoneal injection at doses from 1.25 to 5 mg/kg, as a result of which the average lifespan of animals with a P388 murine leukemia tumor increases from 20 to 28%. Thus, the water-soluble salts of benzofuroxans can be considered as promisingcandidates for further development, both as anti-cancer agents and as stimulants for seed germination and regulators of microflora crop growth