Number Of New Substances Research Articles

Synthesis and antibacterial evaluation of (5Z)-5-[(2-piperidinequinoline-3-yl)methyl]-2-chloroquinoline derivatives: Docking study on substituted N-alkylation and binding mechanisms with E. Coli PDF enzyme

A number of new substances were included into the (5Z)-5-[(2-piperidinequinoline-3-yl)methyl]-2-chloroquinoline structural framework. The condensation process 2-chloroquinoline, which served as a crucial reagent in the reaction with 3-carbaldehydes to produce 2,4-thiazolidinedione, allowed for the production of 1,3-thiazolidine-2,4-dione. The newly developed substances were described by means of their reactions with halide compounds, particularly those pertaining to substituted N-alkylation. Elemental analysis, Fourier-transform infrared spectroscopy (FT-IR), and proton nuclear magnetic resonance spectroscopy (1H NMR) were used to identify the chemical. Furthermore, the antibacterial activity of the produced compounds was evaluated in vitro against a range of pathogens, including Bacillus subtilis, and Escherichia coli. Moreover, docking experiments were conducted using the PDF enzyme of E. coli to improve our understanding of the binding mechanism between the synthesized 5(A-N) compounds and the enzyme.

Particle Size Tailoring of Quercetin Nanosuspensions by Wet Media Milling Technique: A Study on Processing and Formulation Parameters.

A large number of new substances have insufficient biopharmaceutical properties for oral administration caused by their slow dissolution rate and poor solubility. The purpose of our experiment was to improve the physicochemical properties of a hydrophobic drug, quercetin, by the nanomilling approach. Quercetin nanosuspensions were prepared using a wet-milling method followed by lyophilization. Stabilizer type and ratio, drug content, milling time, and bead size were identified as critical variables, and their impacts on quercetin particle size were assessed. The optimized nanocrystal was characterized by its morphology, crystallinity, molecular interactions, saturation solubility, and dissolution properties. At optimized process conditions of milling at 500 rpm for 18 cycles of grinding with 0.3 - 0.4 mm zirconium oxide beads, minimum particle size, and PDI values were 281.21 nm and 0.22, respectively. Nanocrystals showed rod-like nanostructures, and XRD scans confirmed a decrease in drug crystallinity. The optimized formulation showed increased solubility and dissolution rate, as well as good physical stability. Particle size reduction by media milling technique was an efficient method for the solubility enhancement of hydrophobic drugs.

Modeling of Particle Dissolution Behavior Using a Geometrical Phase-Field Approach.

Material dissolution is a critical attribute of many products in a wide variety of industries. The idealized view of dissolution through established prediction tools should be reconsidered because the number of new substances with low aqueous solubility is increasing. Due to this, a fundamental understanding of the dissolution process is desired. The aim of this study was to develop a tool to predict crystal dissolution performance based on experimentally measurable physical parameters. A numerical simulation, called the phase-field method, was used to simultaneously solve the time evolution of the phase and concentration fields of dissolving particles. This approach applies to diffusion-limited as well as surface reaction-limited systems. The numerical results were compared to analytical solutions, and the influence of particle shape and interparticle proximity on the dissolution process was numerically investigated. Dissolution behaviors of two different substances were modeled. A diffusion-limited model compound, xylitol, with a high aqueous solubility and a surface reaction-limited model compound, griseofulvin, with a low aqueous solubility were chosen. The results of the simulations demonstrated that phase-field modeling is a powerful approach for predicting the dissolution behaviors of pure crystalline substances.

Biologics in inflammatory bowel diseases

In addition to conventional anti-inflammatory treatment for chronic inflammatory bowel disease (IBD), there has been an evolution of new treatment options over the past 20 years. Already approved biologics provide multiple treatment alternatives but also make the treatment algorithms more complex. This development results in a substantial improvement in patient care. The ambitious treatment targets are associated with a higher quality of life and the reduction of long-term disability and morbidity. The aim of this article is to give an overview of how biologics can currently be implemented in IBD. In particular, the current clinical management is presented and an outlook on future treatment options with biologics for IBD is provided. A search was carried out in PubMed and ClinicalTrials.gov and the current German and European guidelines and expert recommendations were evaluated. Since the late 1990s there have been a continuously increasing number of treatment options for IBD. All substances have proven safety and efficacy in large randomized clinical studies and enable increasingly more individualized treatment for patients with IBD. Biologics are currently the standard treatment of choice for moderate to severe inflammatory activity as well as for steroid-refractory or steroid-dependent courses of disease after failure of conventional treatment. The diversity of IBD treatment offers increasing treatment options and thus improved patient care; however, as the number of new substances increases treatment becomes more complex. This article summarizes the current and future treatment options for IBD and their integration into current treatment algorithms.

Morphology and quality of beef with regard to a biostimulator used in the diet of animals

The agricultural food industry is currently facing significant challenges. The development of the food industry, biotechnology, chemistry and related sciences has brought a huge number of new substances that can have a negative effect on humans, the level of environmental pollution has increased, which necessitates stricter requirements for food safety. The relevance of the problems of producing organic food, which has recently gone far beyond the boundaries of purely scientific interests, has made them the subject of discussion for various sectors of society. The demand for safe, environmentally friendly and biologically clean, and high-quality food is growing. At the same time, the production of agricultural and food products should be cost-effective. Today, bio-food markets have already formed in the world: these are plant growing products (fruits, vegetables), animal husbandry (dairy products), baby food, and grain. The growth of the cultural level of the population will increase the demand for beef and its processed products. In this regard, the study and search for safe natural components that affect the yield of meat and are able to efficiently convert the energy of food into organic protein are critical. The paper presents the results of studies of beef meat grown using the technology of intensive cultivation using a biostimulator of natural origin. A positive effect of humic natural substances on carcass morphology and beef quality has been proven. An additional reserve to provide an increase in consumer value and production of safe meat raw materials using a natural peat preparation is shown.

Breast Cancer Prevention-Is there a Future for Sulforaphane and Its Analogs?

Breast cancer is the most prevalent type of cancer among women worldwide. There are several recommended methods of breast cancer prevention, including chemoprevention. There are several approved drugs used to prevent breast cancer occurrence or recurrence and metastasizing. There are also a number of new substances undergoing clinical trials and at the stage of initial study. Studies suggest that dietary factors play a crucial role in breast cancer etiology. Epidemiological studies indicate that in particular vegetables from the Brassicaceae family are a rich source of chemopreventive substances, with sulforaphane (SFN) being one of the most widely studied and characterized. This review discusses potential applicability of SFN in breast cancer chemoprevention. A comprehensive review of the literature on the impact of SFN on molecular signalling pathways in breast cancer and breast untransformed cells is presented. The presented results of in vitro and in vivo studies show that this molecule has a potential to act as a preventive molecule either to prevent disease development or recurrence and metastasizing, and as a compound protecting normal cells against the toxic effects of cytostatics. Finally, the still scanty attempts to develop an improved analog are also presented and discussed.

Screening Analysis for Designer Stimulants by LC-MS/MS.

The increase in the number of new substances appearing on the drug market has been observed in the 1980s and 1990s of the last century, when many phenethylamine and tryptamine derivatives entered the market. However, the phenomenon of mass marketing of new designer stimulants (being the components of so-called "legal highs") began to develop since 2006 in Europe, and it was something new. Since then, the number of stimulants introduced on the drug market is growing regularly, rapidly, and intensively. Such a situation creates a need for comprehensive screening methods for detection of these drugs in biological specimens. The fast and simple liquid chromatography-tandem mass spectrometry qualitative screening procedure presented here is designed to detect and identify a wide range of designer stimulants in the blood. The assay has wide applicability for rapid screening of new stimulants in forensic or clinical samples. The procedure can be easily modified for additional novel psychoactive substances.

Phenolic Compounds as Arginase Inhibitors: New Insights Regarding Endothelial Dysfunction Treatment.

Endothelial dysfunction is characterised by the low bioavailability of nitric oxide with a relevant negative impact on the nitric oxide/cGMP pathway. The loss of nitric oxide/cGMP signaling may be caused by an increased arginase activity. Plant-derived substances, especially polyphenols, are compounds that have the potential to inhibit arginase activity and they may represent an attractive therapeutic option to combat clinical outcomes related to endothelial dysfunction. An extensive review was carried out using all available data published in English in the Pubmed database, and without restriction regarding the year of publication. Despite the increased number of new substances that have been tested as arginase inhibitors, it is rare to find a compound that satisfies all the toxicological criteria to be used in the development of a new drug. On the other hand, recent data have shown that substances from plants have great potential to be applied as arginase inhibitors, most of which are polyphenols. Of the relevant mechanisms in this process, the inhibition of arginase by natural products seems to act against endothelial dysfunction by reestablishing the vascular function and elevating nitric oxide levels (by increasing the amounts of substrate (L-arginine, and endothelial nitric oxide synthase activation and stabilisation) as well as decreasing the generation of reactive species (formed by uncoupledendothelial nitric oxide synthase). This review summarises several topics regarding arginase inhibition by natural substances as well as indicating this pathway as an emergent strategy to elevate nitric oxide levels in disorders involving endothelial dysfunction. In addition, some aspects regarding structural activity and future perspectives are discussed.

An in-vitro approach for water quality determination: activation of NF-κB as marker for cancer-related stress responses induced by anthropogenic pollutants of drinking water.

Epidemiological studies show that there is a link between urban water pollution and increase in human morbidity and mortality. With the increase in number of new substances arising from the chemical, pharmaceutical, and agricultural industries, there is an urgent need to develop biological test systems for fast evaluation of potential risks to humans and the environmental ecosystems. Here, a combined cellular reporter assay based on the cellular survival and the stress-induced activation of the survival-promoting factor nuclear factor κB (NF-κB) and its use for the detection of cytotoxicity and cancer-related stress responses is presented. A total of 14 chemicals that may be found in trace-amounts in ground water levels are applied and tested with the presented assay. The project is embedded within the joint research project TOX-BOX which aims to develop a harmonized testing strategy for risk management of anthropogenic trace substances in potable water. The assay identified carbendazim as a NF-κB-activating agent in mammalian cells.

Synthetic cannabinoids abused in South Korea: drug identifications by the National Forensic Service from 2009 to June 2013

The rapid increase in the number of new psychoactive substances and their abuse is the most recent drug abuse issue worldwide. Although abuse of synthetic cannabinoids is highly restricted in South Korea, the rapid increase in the number of new substances is forcing the legal regulation authority to continuously improve the drug regulation act. As a result of drug screening by the National Forensic Service from 2009 to June 2013, 26 species of synthetic cannabinoids were identified in materials seized mainly by the Police Agency and the Prosecutor’s Office in South Korea. One of the most remarkable trends in synthetic cannabinoids is the increase in halogenated derivatives and new substances, including UR-144 and A-836,339 originally developed as analgesics by Abbott Laboratories. The N-pentyl fluorinated analog of UR-144 (XLR-11) has become the most frequently found synthetic cannabinoid in 2013 since its first appearance in 2012, whereas abuse of A-836,339 analogs has been little reported despite their abuse potential. Until early 2011, nicotine was the most frequently found active coingredient with synthetic cannabinoids. However, various psychoactive substances such as Δ9-tetrahydrocannabinol, α-pyrrolidinobutiophenone, α-pyrrolidinovalerothiophenone, and N,N-diallyl-5-methoxytryptamine have often been found as coingredients in herbal highs since late 2011. These coingredients should also be systematically regulated, because they can cause unexpected side effects. It is suggested that authorities in different countries share information about synthetic cannabinoids and their coingredients.

Inadvertent exposure to xenoestrogens in children

This article reviews previous studies and presents new data on pesticide exposure in order to provide some indications of the extent and significance of childhood exposure to xenoestrogens, including pesticides, epoxy resins, and polycarbonates. After more than four decades of pesticide use, little is known about their adverse effects on health. There is a need to address the potential risks associated with the current contamination of water, soils, and foods in many agricultural areas. In southeastern Spain, along the Mediterranean coast, extensive areas alongside residential zones are devoted to intensive farming in plastic greenhouses, with the use of large amounts of pesticides. Human tissue samples have been investigated for pesticide residues. Samples of fat from children living in farm areas contained a total of 14 pesticides, including lindane, HCH, heptachlor, aldrin, dieldrin, endrin, endosulfan, o,p′-DDE, and o,p′-DDD, among others. Of the 113 samples studied, 43 were positive for one or more pesticides, some of which have estrogenic activity. The number of new substances that mimic the action of endogenous estrogens is increasing rapidly. These endocrine-disrupting chemicals are not restricted to pesticides. Several different compounds used in the food industry, in plasticizers, and in dental restorations are also estrogenic. The few studies that have investigated their effects in humans all indicate that concerns are warranted. If there is indeed an association between zexposure to substances with hormone-disruptive activity and certain disorders of sexual maturation, the incidence of such disorders should be greater in areas where exposure to agents with this activity is high. We used a spatial ecological design to search for variations in orchidopexy rates and to analyze relationships between these differences and geographical variations in exposure to pesticides. Our results are compatible with a hypothetical association between exposure to hormone-disruptive chemicals and the induction of cryptorchidism. Several methodological limitations in the study design make it necessary to evaluate the results with caution. In conclusion, a closer scrutiny is required to determine whether epoxy resins and polycarbonates contribute, together with estrogenic pesticides, to the exposure of human consumers, especially children, to xenoestrogens.

Inadvertent exposure to xenoestrogens in children.

This article reviews previous studies and presents new data on pesticide exposure in order to provide some indications of the extent and significance of childhood exposure to xenoestrogens, including pesticides, epoxy resins, and polycarbonates. After more than four decades of pesticide use, little is known about their adverse effects on health. There is a need to address the potential risks associated with the current contamination of water, soils, and foods in many agricultural areas. In southeastern Spain, along the Mediterranean coast, extensive areas alongside residential zones are devoted to intensive farming in plastic greenhouses, with the use of large amounts of pesticides. Human tissue samples have been investigated for pesticide residues. Samples of fat from children living in farm areas contained a total of 14 pesticides, including lindane, HCH, heptachlor, aldrin, dieldrin, endrin, endosulfan, o,p'-DDE, and o,p'-DDD, among others. Of the 113 samples studied, 43 were positive for one or more pesticides, some of which have estrogenic activity. The number of new substances that mimic the action of endogenous estrogens is increasing rapidly. These endocrine-disrupting chemicals are not restricted to pesticides. Several different compounds used in the food industry, in plasticizers, and in dental restorations are also estrogenic. The few studies that have investigated their effects in humans all indicate that concerns are warranted. If there is indeed an association between zexposure to substances with hormone-disruptive activity and certain disorders of sexual maturation, the incidence of such disorders should be greater in areas where exposure to agents with this activity is high. We used a spatial ecological design to search for variations in orchidopexy rates and to analyze relationships between these differences and geographical variations in exposure to pesticides. Our results are compatible with a hypothetical association between exposure to hormone-disruptive chemicals and the induction of cryptorchidism. Several methodological limitations in the study design make it necessary to evaluate the results with caution. In conclusion, a closer scrutiny is required to determine whether epoxy resins and polycarbonates contribute, together with estrogenic pesticides, to the exposure of human consumers, especially children, to xenoestrogens.

Structural properties of economic systems and health risks.

Increasing amounts of money and manpower are spent to set standards for toxic sub-stances that may endanger the health of workers. Numerous publications refer to areas where facts and insights are increasing. Notwithstanding this, however, only a relatively small number of scientific findings turn out to belong unrestrictedly to the area of health policy within labour organizations. Among the number of suspect substances, only a few are subjected to undisputed norms and/or are accepted as hazardous and really undesirable. On the other hand, the number of new substances, constantly introduced into our lives, that we know little or nothing about is overwhelming.

Influence of 1-double bond and 11β-hydroxy group on stereospecific microbial reductions of 4-en-3-oxo-steroids

The yeast Rhodotorula glutinis and the anaerobic bacterium Clostridium paraputrificum were used for stereospecific reductions of 4-chloro-11β-hydroxy-17α -methyl-testosterone and the corresponding 1-dehydro compound to prepare 5α- and 5β-H derivatives, respectively. C. paraputrificum was able to 5β-reduce both substances, whereas the 5α-reduction by R. glutinis was inhibited by the structure elements 1-en and 11β-OH so that the substrate with both structure elements was not 5α-reduced. The microbial conversion of the four steroids with and without 1-en and 11β-OH was compared in semiquantitative experiments. A number of new substances are described, 11β-hydroxy and 11-oxo derivatives of 5α- and 5β-dihydro-4-chloro-17g-methyltestosterone including some 3-OH compounds and characterized by NMR, mass spectrometric and further data.

Halogen Substituted 1,3‐Cyclohexanediones II. New Chlorinated Cycloalkanones from 2, 2‐Dichlorodimedone

AbstractA number of new substances obtained from 2,2‐dichlorodimedone are described. The most interesting features of the reactions are: a) the ring contraction to a 2‐cyclopentenone derivative with simultaneous carbon monoxide elimination, b) the isomerization procedure of halogenated ketones in dimethylformamide and hydrogen chloride, c)the aromatization to some new resorcinol derivatives. The high yields give most of the procedures a distinct preparative interest.

Aspects of High Polymeric Chemistry

INTRODUCTION WHEN the magnificent structure known as organic chemistry was built up in the second half of last century, it contained not only an enormous number of new substances with interesting and valuable properties, but also embodied a series of more or less general laws on the relations between the structure and the qualities of a molecule. It was realized, for example, that the presence of certain atomic groups (OH, NH2, HSO3) had as a consequence solubility in water, that other combinations of atoms impressed on the molecule the property of a dyestuff, others again made it a narcotic, or an explosive, and so on. These laws did not appear suddenly in clear and definite shape, but grew slowly with the development of chemical science. They were nearly all formulated at first as preliminary rules, and their validity checked by the aid of the continually increasing experimental material. Some of them did not successfully pass this test; they are forgotten to-day and many of them are no longer known; others have survived and represent our present knowledge of the possibilities of constructing a molecule with required properties. They can be called the leading principles of preparative organic chemistry, and are of utmost value for all synthetic work in chemical industry.