Nitrogen Derivatives Research Articles

Discovery of nitrogenous derivatives of dihydromyricetin in cell culture medium

AbstractDihydromyricetin (DMY) is a health‐beneficial flavanonol in the family of flavonoids, extracted from Ampelopsis grossedentata (Hand.‐Mazz.) W. Wang. When investigating the stability of DMY in Dulbecco's modified Eagle's medium (DMEM) solution at 37°C by LC‐MS/MS, four nitrogenous derivatives of DMY were found except for the previously known dimers, oxidized products, and ring‐cleavage products of DMY. Compound 1 (N‐DMY) was identified to be 4′‐amino (NH2)‐DMY based on MS and NMR data. The formation mechanism of N‐DMY was thought to include two steps. First, the pyrogallol moiety on the ring B of DMY was prone to be oxidized to quinone. Second, quinone might further participate in the Strecker degradation of amino acids in DMEM to form N‐DMY and corresponding aldehydes. Correspondingly, compounds 2–4 might be formed by the Strecker degradation reaction of amino acids in DMEM with quinones from the oxidation of DMY dimers and DMY ring‐cleavage products. Consistent with the formation mechanism, it was observed that flavonoids with a catechol or pyrogallol moiety readily form their nitrogenous derivatives during the incubation in DMEM at 37°C, which might be because catechol or pyrogallol are easily oxidized to quinones. In addition, the nitrogenous derivatives of flavonoids may have a potential to participate in the metabolism of flavonoids during in vitro and in vivo experiments. Therefore, flavonoid nitrogenous derivatives may play a significant role in the actual effects of flavonoids, which need to be further investigated in the future.

Chemometric and risk assessment of nitrogen composition of atmospheric rainwater from diverse surfaces in Rivers State, Nigeria.

Organic and inorganic nitrogen ions in the environment play important role across environmental matrices. Rainwater samples collected from ambient and different roofing surfaces (zinc, aluminium, asbestos and stone-coated roofing sheets) from selected locations at Ogale, Rumuodomaya/Rumuodome, Diobu and Chokocho within Rivers State, Niger Delta, Nigeria, from April to June, July to August and September to October depicting three regiments of early, mid and late rains. The samples were analysed for Kjeldahl nitrogen, ammonium, nitrate and nitrite using APHA methodology. Quantitative assessment showed that Kjeldahl nitrogen were in range of 0.11 to 28.05mg/L; ammonium 0.50 to 20.22mg/L, nitrate from 0.12 to 22.69mg/L and nitrite from 0.15 to 3.90mg/L. Parameters decreased from early to late rain, which can be attributed to rain dilution factor potential, wind pattern and emission from anthropogenic sources that influenced the rainwater quality across surfaces. Nitrogen results showed that dry and wet deposition has great impact; atmospheric aerosols and biogeochemical interactions can affect water quality. Monthly variation showed that Ogale had high regression compared to other locations due to close proximity to oil and gas emission and marine contribution. Neutralization factor showed that nitrate-nitrite compounds have strong correlation with ammonium ion. Non-carcinogenic risk assessment using US EPA model showed hazard index less than one (1), thus no associated health effect of nitrate and nitrite in rainwater. In conclusion, it is evident that nitrate/nitrite levels and other nitrogen derivatives in rainwater in crude oil-producing Niger Delta and its continuous consumption can cause negative health outcome.

Ameliorative effects of zeolite and yucca extract on water quality, growth performance, feed utilization, and hematobiochemical parameters of European seabass reared at high stocking densities

The aim of the present study was to evaluate the efficiency of natural zeolite (Z) and Yucca schidigera extract (YE) as water treatments for European seabass, Dicentrarchus labrax, reared at high stocking density. A factorial design was conducted using two socking densities (100 and 200 fingerlings/m3) and five water treatments (control, zeolite 10 g/L, zeolite 15 g/L, YE 0.75 ml/l, and YE 1 ml/L). The fish (with an initial weight of 5.83 g) were allocated into 1 m3 fiberglass tanks in triplicates per each treatment and fed a commercial diet for 45 days. The results demonstrated that rearing European seabass at a high stocking density (200 fish/m3) caused a significant deterioration in water quality parameters, such as dissolved oxygen, NH3-N, NH4-N, NO2-N, and NO3-N by 11.11 %, 49.5 %, 33.33 %, 38.46 %, and 9.09 %, respectively compared to the low stoking density. Furthermore, increasing the stocking density of European seabass significantly reduced growth performance, feed utilization, and various haemato-biochemical parameters. The water treatment with both zeolite and YE significantly improved dissolved oxygen levels and decreased the nitrogen derivatives in tanks water of low and high stocking densities. Also, the water treatments ameliorated the effects of increasing stocking density on fish growth performance, feed utilization, hematological, and biochemical parameters. Whereas the highest wight gain (32.17 g), survival (93 %), and best FCR (1.9) were recorded in group treated with high zeolite level at low stocking density. Regarding the efficiency of both water treatment materials used in this study, water treatment with zeolite at the highest level (15 g/L) outperformed YE in different evaluated parameters of water quality, fish growth, and physiological performance. The mean effects of zeolite and YE at high levels showed an improvement of weight gain and feed conversion ratio by 103.68 %, 46.37 %, 30.90 %, and 23.47 %, respectively, compared to the control. Moreover, the effects of each substrate were level dependent. In conclusion, the water treatment with zeolite and YE could improve the wellbeing and production of seabass fish in favor of zeolite (15 g/l).

Copper (II) complexes with N, S donor pyrazole-based ligands as anticancer agents.

A group of bidentate nitrogen and sulfur donor pyrazole derivative ligands abbreviated as Na[RNCS(Pz)], Na[RNCS(PzMe2)], Na[RNCS(PzMe3)], Na[RNCS(PzPhMe)], Na[RNCS(PzPh2)], where (R = Et, Ph), and their Cu (II) complexes were synthesized and characterized by spectroscopic and physicochemical methods. The crystal structure of [Cu(PhNCSPzMe3)2] was determined by X-ray crystallography analysis and the results described a distorted square planar coordination geometry for this complex. Also, the cyclic voltammetry investigations indicated that the synthesized copper complex is an electrochemically active species. Moreover, the cytotoxic activity of all of the twenty synthesized compounds was evaluated using MTT assay against the MCF-7 (human breast carcinoma) cell lines, in vitro. Cu (II) complexes indicate significant cytotoxicity against the MCF-7 cell lines as compared with the free ligands. The docking studies showed that the copper complexes have better interactions with EGFR and CDK2 proteins, compared to the free ligands, and most of the studied compounds have a higher value of binding energy relative to the studied controls. The results of QSAR analysis suggest that dipole moment is in direct correlation with the obtained IC50 values, and it strongly impact the anticancer effects generated by the compounds. Our findings suggest that the developed copper complexes can be good candidates for further evaluations as chemotherapeutic agents in the treatment of cancer.

Synthesis, biological evaluation and molecular docking studies of novel diosgenin derivatives as anti-inflammatory agents

Thirty-two novel DG F-spiroacetal ring-opening derivatives, including 24 acetylated derivatives and 8 nitrogenous derivatives, were designed and synthesized from diosgenin (DG). The cytotoxicity of the novel derivatives was evaluated by MTT assay, except for compounds 4a, 4e, 4i, 4 l, 5a and 5 h, which were potentially cytotoxic to RAW264.7 cells, all the other derivatives had no significant cytotoxicity. The NO release inhibitory activities of novel derivatives were screened by Griess method. The results showed that the anti-inflammatory activity of the DG acetylated derivatives was stronger than the nitrogenous derivatives, and 4a-4 m containing acetyl groups at the 3-position may have better anti-inflammatory effects than 5a-5 k containing free hydroxyl groups. In ELISA assay, compound 4 m exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by LPS with IC50 values 0.449 ± 0.050 μM. The results of docking experiments showed that 4 m has a good affinity for p65 protein.

Synthesis, biological evaluation and mechanism studies of C-3 substituted nitrogenous heterocyclic 23-Hydroxybetulinic acid derivatives as anticancer agents

A series of novel nitrogenous heterocycle substituted 23-Hydroxybetulinic acid (23-HBA) derivatives with amide linkages at the C-3 position were designed, synthesized and evaluated for their antitumor activities. The biological screening results showed that most of the derivatives exhibited more potent antiproliferative activities than 23-HBA. In particular compound II-9 exhibited the most potent activities with IC50 values ranging from 1.96 μM to 6.20 μM against five cancer cell lines (B16, HepG2, A2780, MCF-7 and A549). The preliminary mechanism study showed that compound II-9 caused cell cycle arrest at G1 phase, induced cell apoptosis and depolarized mitochondria of B16 cells in a dose dependent manner. Moreover, western blot analysis indicated that compound II-9 down-regulated the expression of anti-apoptotic protein Bcl-2, up-regulated the expression of pro-apoptotic protein Bad, and activated cytochrome C and caspase 3 to cause cell apoptosis. In summary, II-9 may serve as a promising lead for the development of new natural product-based antitumor agents and deserve further investigation.

Semisynthetic triterpenes led to the generation of selective antitrypanosomal lead compounds.

Triterpenes α,β-amyrin are naturally occurring molecules that can serve as building blocks for synthesizing new chemical entities. This study synthesized acyl, carboxyesther, NSAID, and nitrogenous derivatives and evaluated their antimicrobial activity. A cyclodextrin complexation method was developed to improve the solubility of the derivatives. Of the 17 derivatives tested, five exhibited activity against Trypanosoma cruzi, T. brucei, Leishmania infantum, Candida albicans, Staphylococcus aureus, and Escherichia coli. The 9a/9b mixture showed weak activity against the parasites (IC50 24.45-40.32μM). However, it showed no activity for the other microorganisms. Derivatives 14a/14b exhibited potent activity against T. cruzi (IC50 2.0nM) in this tested concentration did not show activity to the other microorganisms and were not cytotoxic. Derivatives 15a/15b and 16a/16b demonstrated relevant activity against the parasites (IC50 2.24-5.44μM), but were also cytotoxic. Derivatives 17a/17b showed low activity against the tested parasites (IC50 21.70-22.79μM), but they were selective since they did not show activity against other microorganisms. In docking studies, in general, all derivatives showed complementarity with the CYP51 binding site of the trypanosomatid mainly by hydrophobic interactions; thus, it is not conclusive that the molecules act by inhibiting this enzyme. Our results showed that triterpenes derivatives with antitrypanosomal activity could be synthesized by an inexpensive and rapid method.

Oxidative Stress and Redox Signaling in the Pathophysiology of Liver Diseases.

The increased production of derivatives of molecular oxygen and nitrogen in the form of reactive oxygen species (ROS) and reactive nitrogen species (RNS) lead to molecular damage called oxidative stress. Under normal physiological conditions, the ROS generation is tightly regulated in different cells and cellular compartments. Any disturbance in the balance between the cellular generation of ROS and antioxidant balance leads to oxidative stress. In this article, we discuss the sources of ROS (endogenous and exogenous) and antioxidant mechanisms. We also focus on the pathophysiological significance of oxidative stress in various cell types of the liver. Oxidative stress is implicated in the development and progression of various liver diseases. We narrate the master regulators of ROS-mediated signaling and their contribution to liver diseases. Nonalcoholic fatty liver diseases (NAFLD) are influenced by a "multiple parallel-hit model" in which oxidative stress plays a central role. We highlight the recent findings on the role of oxidative stress in the spectrum of NAFLD, including fibrosis and liver cancer. Finally, we provide a brief overview of oxidative stress biomarkers and their therapeutic applications in various liver-related disorders. Overall, the article sheds light on the significance of oxidative stress in the pathophysiology of the liver. © 2022 American Physiological Society. Compr Physiol 12:3167-3192, 2022.

Recent Progress in Luminescent Cu(I) Halide Complexes: A Mini-Review.

Copper(I) halide complexes are well sought-after materials due to their rich structural diversities and photophysical properties. Profoundly, there is a direct relationship between each structural variation and luminescence of these complexes, for a purported use. In this review, recent publications within the last 2 years about copper(I) halide complexes, centering on their structural dimensionalities with derivatives of nitrogen, phosphorus, and sulfur ligands, have been considered alongside their effects on luminescence.

Antifungal mono- and dimeric nitrogenous bisabolene derivatives from a sponge in the order Bubarida from Futuna Islands.

An abundant sponge of the order Bubarida was selected for further chemical investigation following biological and chemical screening of sponges collected from Futuna Islands in the Indo-Pacific. Ten new nitrogenous bisabolene derivatives were isolated and identified: the monomeric theonellin formamide analogues named bubaridins A-F (1-6) with unusual oxidised linear chains, and the first isocyanide/formamide dimeric and cyclised bisabolenes 7-9. The structure elucidation of these nitrogenous bisabolenes involved HRESIMS, NMR, and ECD analyses, and the chiral compounds were found to be racemates. A biosynthetic hypothesis for the production of these metabolites is proposed and some chemotaxonomic considerations are discussed. Furthermore, the antimicrobial and antitumoral activity were evalutated and the trans-dimer theonellin isocyanide (7) was shown to exhibit potent and selective antifungal activity.

Understanding the higher–order cycloaddition reactions of heptafulvene, tropone, and its nitrogen derivatives, with electrophilic and nucleophilic ethylenes inside the molecular electron density theory

The reactivity and selectivity in higher–order cycloadditions of cycloheptatrienes A–D with ethylenes E–G are studied within the MEDT.

Synthesis, Biological Evaluation and Mechanism Studies of C-3 Substituted Nitrogenous Heterocyclic 23-Hydroxybetulinic Acid Derivatives as Anticancer Agents

Synthesis, Biological Evaluation and Mechanism Studies of C-3 Substituted Nitrogenous Heterocyclic 23-Hydroxybetulinic Acid Derivatives as Anticancer Agents

Bay-Dissymmetrical hetero- and Aza-Benzannulated PeryleneDiimides as new n-type semiconductors

AzaBenzannulated PeryleneDiimides (AzaBPDIs) and their nitrogen, sulphur and seleniumbay-functionalized derivatives are introduced herein as a new class of n-type semiconductors.

Boron, silicon, nitrogen and sulfur-based contemporary precursors for the generation of alkyl radicals by single electron transfer and their synthetic utilization.

Recent developments in the use of boron, silicon, nitrogen and sulfur derivatives in single-electron transfer reactions for the generation of alkyl radicals are described. Photoredox catalyzed, electrochemistry promoted or thermally-induced oxidative and reductive processes are discussed highlighting their synthetic scope and discussing their mechanistic pathways.

A Molecular Docking Studies of a Few of Derivatives of Nitro Ketene Dithiols , Decalin-β-keto Ester Enolate and Furo Pyrazole Derivatives for Mycobacterium Tuberculosis

Tuberculosis (TB) is a common and often mortal bacterial infectious disease caused by constrains pathogens (Mycobacterium). The present study is about the in silico drug screening of 75 (Nitrogen, sulfur, and oxygen-containing) derivatives of Nitroketen dithiol, decalin-β- keto ester enolate, and Furo pyrazole to control the viral growth by blocking the active site of Tuberculosis protein 1L9U. After docking 75 ligand molecules, three hits were selected based on the binding affinities. Lipinski’s rule, the hydrogen bonding, and drug-likeness were also investigated for their potentiality as suitable drug candidates. The present analysis identifies three derivatives of nitro ketene dithiol, which can be used as a potentially better drug candidate to the commercial drug Rifampicin, which is used for the treatment of Tuberculosis. These three compounds have better binding and drug properties with a simple structure; it is of interest to consider them for further in-vitro and in vivo evaluation to declare them as better drug candidates for TB.

Efeitos do ácido ricinoleico do óleo de mamona e do líquido da castanha de caju sobre a digestibilidade de nutrientes e fermentação ruminal de novilhas leiteiras

ABSTRACT This study aimed to evaluate the effects of combining functional oils (FO) [ricinoleic acid (RA) and cashew nutshell liquid (CNSL)] on nutrient intake and total-tract apparent digestibility, ruminal fermentation, nitrogen utilization, and predicted rumen microbial protein (Pmic) in heifers. Twelve Jersey heifers (14±0.6 months and 264±18.7 kg BW) were assigned to a 4 × 4 Latin square experiment with the following treatments: Control (CON), diet without feed additives; Ricinoleic acid, dietary inclusion of RA at 2 g kg-1 dry matter (DM); Cashew nutshell liquid, dietary inclusion of CNSL at 2 g kg-1 DM; and a mixture of 1 g kg-1 DM of RA and 1 g kg-1 DM of CNSL (RA+CNSL). Heifers were allowed 14 d for treatment adaptation followed by 5 days of sampling. Total feces collection was performed to determine digestibility. Rumen fluid was collected to determine short-chain fatty acids (SCFA) concentration. Urine samples were collected for nitrogen and purine derivatives analyses. Feeding RA decreased intake of DM, but increased crude protein (CP) digestibility and ruminal acetate concentration. Feeding CSNL increased NDF digestibility and lowered Pmic. The association of RA+CNSL increased neutral detergent fiber (NDF) digestibility and ruminal concentration of total SCFA without affecting DM intake. Feeding RA treatment decreased N intake and N excreted in feces and urine. CNSL group had the highest values of N balance. Heifers fed RA had lower Pmic than CNSL and RA+CNSL. The association of RA+CNSL improved digestibility of fiber and increased ruminal concentration of SCFA without altering N balance and Pmic.

The antioxidant defense responses of Hordeum vulgare L. to polycyclic aromatic hydrocarbons and their derivatives in biochar-amended soil

The recent studies indicated that the biochar (BC) may be a source of polycyclic aromatic hydrocarbons (PAHs) as well as their oxygen, nitrogen, or sulfur-containing derivatives that are considered as more toxic pollutants than their parent compounds. Here, the assessment of the impact of various biochars addition (1% wt.) to soil on barley Hordeum vulgare L. growth was presented. The concentrations of bioavailable PAHs and their derivatives in biochar were determined. PAHs increased reactive oxygen species generation resulting in oxidative stress in organisms. In this study, the response of soil-grown plants was examined in terms of the activity of the antioxidative enzymes (superoxide dismutase, catalase, peroxidase), lipid peroxidation, and the expression of genes related to oxidative stress. The results indicate that despite low content of a bioavailable fraction of parent compounds and their derivatives (up to 4.45 ± 0.24 ng gbiochar−1 and 0.83 ± 0.03 ng L−1, respectively) the biochemical response of plant was present, the activity of superoxide dismutase increased up to 2 times, but the activity of the other enzymes was lowered. The transcript level values support the studies on enzymatic activity. The presence of PAHs and their derivatives induced oxidative stress slightly but the plant was able to mitigate it.

Synthesis of Heterospirocycles through Gold‐(I) Catalysis: Useful Building Blocks for Medicinal Chemistry

AbstractGold‐(I) catalysis was used for the intramolecular cyclization of tertiary alcohols with terminal alkynes to form diverse aza‐spirocycles. The reaction was carried out with low catalyst loading under microwave irradiation to give both sulfonylated and acylated spirocyclic nitrogen derivatives. Gram scale spirocyclization was carried out to demonstrate the robustness of the reaction. An intramolecular Mizoroki‐Heck reaction was performed to give several tetracyclic spirocycles. Double bond reduction and selective protecting group manipulation gave spiropiperazine and spiromorpholine derivatives. These compounds were incorporated into biologically relevant scaffolds to give the first selective spirocyclic inhibitors of LIMK1.magnified image

Electrifying the nitrogen cycle: An electrochemical endeavor

The advent of the Haber–Bosch (HB) process has made accessible all forms of nitrogenous derivatives (ammonia, nitrates, nitrites, and amines), revolutionizing the chemical industry. However, the depleting natural resources and growing environmental concerns demand a shift toward an energy-abated and environment-friendly alternative to the HB process, hence the shift in the recent research focus. The electrochemical reduction pathway offers one of the most alluring prospects as a carbon-free, environment-friendly, energy-abated alternative to the HB process. In this context, we provide a holistic overview of the electrochemical pathways for nitrogen fixation into its activated forms and categorically discuss the energetical and technological challenges that researchers encounter, simultaneously highlighting commendable contributions in the field. We also propose research targets that can serve as a benchmark to measure progress toward the practical realization of the electrochemical nitrogen reduction reaction.

81. Effect of benzoic acid supplementation in pig diets on the pH, nitrogen derivatives and ammonia emission of pig excretions during storage

81. Effect of benzoic acid supplementation in pig diets on the pH, nitrogen derivatives and ammonia emission of pig excretions during storage