Amino Derivatives Research Articles

Metabolomics reveal metabolic variation caused by co-culture of Arthrobacter ureafaciens and Trichoderma harzianum and their impacts on wheat germination.

Arthrobacter ureafaciens DnL1-1 is a bacterium used for atrazine degradation, while Trichoderma harzianum LTR-2 is a widely used biocontrol fungus. In this study, a liquid co-cultivation of these two organisms was initially tested. The significant changes in the metabolome of fermentation liquors were investigated based on cultivation techniques (single-cultured and co-cultured DnL1-1 and LTR-2) using an UPLC-QTOF-MS in an untargeted metabolomic approach. Principle components analysis (PCA) and partial least squares discriminant analysis (PLS-DA) supervised modelling revealed modifications of the metabolic profiles in fermentation liquors as a function of interactions between different strains. Compared with pure-cultivation of DnL1-1, 51 compounds were altered during the cocultivation, with unique and significant differences in the abundance of organic nitrogen compounds (e.g. carnitine, acylcarnitine 4:0, acylcarnitine 5:0, 3-dehydroxycarnitine and O-acetyl-L-carnitine) and trans-zeatin riboside. Nevertheless, compared with pure-cultivation of LTR-2, the abundance of 157 compounds, including amino acids, soluble sugars, organic acids, indoles and derivatives, nucleosides, and others, changed significantly in the cocultivation. Among them, the concentration of tryptophan, which is a precursor to indoleacetic acid, indoleacetic acid, aspartic acid, and L-glutamic acid increased while that of most soluble sugars decreased upon cocultivation. The fermentation filtrates of co-cultivation of LTR-2 and DnL1-1 showed significant promoting effects on germination and radicle length of wheat. A subsequent experiment demonstrated synergistic effects of differential metabolites caused by co-cultivation of DnL1-1 and LTR-2 on wheat germination. Comprehensive metabolic profiling may provide valuable information on the effects of DnL1-1 and LTR-2 on wheat growth.

Role of Aminated Derivatives of Natural Gum in Release Modulating Matrix System of Losartan Potassium

Objective: The investigation aimed to synthesize amino derivatives of various natural gums like Xanthan gum and Tamarind gum for using them as a release modulating polymer in the formulation of the hydrophilic matrix system of losartan potassium and to find the best amongst them. Developing oral sustained release matrix tablets for a drug with a constant release rate has always been a challenge to the pharmaceutical technologist. 
 Materials and Methods: Release modulating hydrophilic matrix tablets of losartan potassium were prepared by wet granulation method. A total number of 6 formulations of release modulating hydrophilic matrix tablets of losartan potassium were prepared using different polymeric ratios of Carbopol 934, aminated Tamarind gum and aminated Xanthan gum based on preliminary trial bathes. The formulated tablets were evaluated for both pre-compression and post-compression evaluation studies. 
 Results: Based on in vitro drug release study the effective formulations AXG 3 are shows a maximum similar release profile to other remains formulations with a theoretical drug release profile of losartan potassium for sustained release. Finally optimized formulation AXG 3 containing carbopol 934 (60 mg), aminated xanthan gum (40 mg), MCC (190 mg) and magnesium stearate (10 mg) showed 100±0.024 % drug release in 12 hr which is acceptable with theoretical drug release of losartan potassium for sustain release dose. Conclusion: Aminated derivatives of xanthan gum and Tamarind gum extend the drug release for 12 hr. Based on in vitro drug release studies of formulations, we concluded that the alteration in the concentration of carbopol 934 with an aminated derivative of xanthan gum in sustain release formulation development was more effective and economical.

Synthesis and evaluation of the antioxidant activity of amino derivatives of o-isobornylphenols

Synthesis and evaluation of the antioxidant activity of amino derivatives of o-isobornylphenols

Integrated metabolomics and transcriptomics reveal metabolites difference between wild and cultivated Ophiocordyceps sinensis

Ophiocordyceps sinensis is a traditional medicinal fungus endemic to the alpine and high-altitude areas of the Qinghai-Tibet plateau. The scarcity of the wild resource has led to increased attention to artificially cultivated O. sinensis. However, little is known about the metabolic differences and the regulatory mechanisms between cultivated and wild O. sinensis. This study exploited untargeted metabolomics and transcriptomics to uncover the differences in accumulated metabolites and expressed genes between wild and cultivated O. sinensis. Metabolomics results revealed that 368 differentially accumulated metabolites were mainly enriched in biosynthesis of amino acids, biosynthesis of plant secondary metabolites and purine nucleotide metabolism. Cultivated O. sinensis contained more amino acids and derivatives, carbohydrates and derivatives, and phenolic acids than wild O. sinensis, whereas the contents of most nucleosides and nucleotides in wild O. sinensis were significantly higher than in cultivated O. sinensis. Transcriptome analysis indicated that 4430 annotated differentially expressed genes were identified between two types. Integrated metabolomics and transcriptomics analyses suggested that IMPDH, AK, ADSS, guaA and GUK genes might be related to the synthesis of purine nucleotides and nucleosides. Our findings will provide a new insight into the molecular basis of metabolic variations of this medicinal fungus.

Nitrogen fixation capacity and metabolite responses to phosphorus in soybean nodules

Phosphorus (P) is necessary for nitrogen fixation in the root nodules of soybeans, a symbiotic process whereby plants support bacterial nitrogen fixation to obtain nitrogen needed for plant growth. Nitrogen accumulation, quantity, weight, specific nitrogenase activity (SNA) and acetylene reduction activity (ARA) of root soybean nodules were analyzed, using a broadly targeted metabolomics method incorporating liquid chromatography-mass spectrometry (LC-MS) to study the effects of P level (1, 11, 31, 61 mg/L denoted by P1, P11, P31, P61) on the types and abundance of various metabolites and on the expression of associated metabolic pathways in soybean root nodules. Nitrogen accumulation, quantity, weight, SNA and ARA of root nodules were inhibited by P stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that root nodules responded to P stress by increasing the number of amino acids and derivatives. Down-regulation of ABA, phosphorylcholine, and D-glucose 6-phosphate affected carotenoid biosynthesis, glycerophospholipid metabolism and sugar metabolism which inhibited nodule nitrogen fixation under P stress. More flavonoids were involved in metabolic processes in soybean root nodules under P stress that regulated the nodulation and nitrogen fixation. The pathway ascorbate and aldarate metabolism, and associated metabolites, were involved in the adaptation of the symbiotic soybean root nodule system to P starvation. This work provides a foundation for future investigations of physiological mechanisms that underly phosphorus stress on soybeans.

Combined Metabolomic and Quantitative RT-PCR Analyses Revealed the Synthetic Differences of 2-Acetyl-1-pyrroline in Aromatic and Non-Aromatic Vegetable Soybeans

Aroma is an important economic trait of vegetable soybeans, which greatly influences their market value. The 2-acetyl-1-pyrroline (2AP) is considered as an important substance affecting the aroma of plants. Although the 2AP synthesis pathway has been resolved, the differences of the 2AP synthesis in the aromatic and non-aromatic vegetable soybeans are unknown. In this study, a broad targeted metabolome analysis including measurement of metabolites levels and gene expression levels was performed to reveal pathways of aroma formation in the two developmental stages of vegetable soybean grains [35 (S5) and 40 (S6) days after anthesis] of the 'Zhexian No. 8' (ZX8, non-aromatic) and ZK1754 (aromatic). The results showed that the differentially accumulated metabolites (DAMs) of the two varieties can be classified into nine main categories including flavonoids, lipids, amino acids and derivatives, saccharides and alcohols, organic acids, nucleotides and derivatives, phenolic acids, alkaloids and vitamin, which mainly contributed to their phenotypic differences. Furthermore, in combination with the 2AP synthesis pathway, the differences of amino acids and derivatives were mainly involved in the 2AP synthesis. Furthermore, 2AP precursors' analysis revealed that the accumulation of 2AP mainly occurred from 1-pyrroline-5-carboxylate (P5C), not 4-aminobutyraldehyde (GABald). The quantitative RT-PCR showed that the associated synthetic genes were 1-pyrroline-5-carboxylate dehydrogenase (P5CDH), ∆1-pyrroline-5-carboxylate synthetase (P5CS), proline dehydrogenase (PRODH) and pyrroline-5-carboxylate reductase (P5CR), which further verified the synthetic pathway of 2AP. Furthermore, the betaine aldehyde dehydrogenase 2 (GmBADH2) mutant was not only vital for the occurrence of 2AP, but also for the synthesis of 4-aminobutyric acid (GABA) in vegetable soybean. Therefore, the differences of 2AP accumulation in aromatic and non-aromatic vegetable soybeans have been revealed, and it also provides an important theoretical basis for aromatic vegetable soybean breeding.

An Endogenous Metabolic Modulator Composition Improves Hydration Status and Decreases Adhesion Properties of Red Blood Cells from Patients with Sickle Cell Disease

Background Sickle cell disease (SCD) is a group of hemoglobinopathies caused by point mutations in the β-globin gene leading to abnormal red blood cells (RBCs). There are various forms of SCD; sickle cell anemia (SCA) is characterized by homozygosity for hemoglobin (Hb) S (HbSS) whereas HbSC disease results from compound heterozygosity for HbS and HbC. HbC does not lead to RBC sickling, but induces loss of intracellular K+ and H2O causing RBC dehydration. Similarly, in HbSS RBCs, through dehydration, an increase of the intracellular concentration of poorly soluble HbS enhances polymerization upon deoxygenation, causing RBCs to become rigid and to sickle. Until recently, the only approved therapy for SCD was hydroxyurea (HU). HU increases fetal Hb (HbF) levels and improves RBC hydration and deformability. For decades, amino acids have been explored as potential treatment to restore the disrupted pathophysiological pathways in SCD. RCitNacQCarLKHVS, an Endogenous Metabolic Modulator (EMM) composition of ten different amino acids and derivatives, was designed to target and support RBC metabolism. In this study, we investigated the effect of ex vivo treatment of this EMM on RBC properties and function in SCA and HbSC. Methods Blood of 12 different adult SCD patients (9 HbSS [of whom 6 were on chronic RBC exchange (RBCX)], 3 HbSC) and 2 healthy controls was collected. Whole blood was incubated at standardized hematocrit (20%, patient plasma) in the presence or absence of different RCitNacQCarLKHVS concentrations for 4h at 37°C. Routine hematological parameters were measured using the Cell-Dyn Sapphire (Abbott Diagnostics). Percentage of total dense RBCs (%DRBCs) was analyzed from 10/12 patients (4 HbSS on RBCX, 3 HbSS not on RBCX, 3 HbSC) using the Advia 120/2120 hematology analyzer (Siemens Healthcare Diagnostics). Point of sickling (PoS), RBC deformability (EImax), and hydration status (Ohyper) were assessed by oxygen gradient ektacytometry and osmotic gradient ektacytometry, respectively, in 12/12 patients using the Lorrca (RR Mechatronics). Blood viscosity was measured in 6/12 patients (3 HbSS not on RBCX and 3 HbSC) at 37°C using a cone-plate viscometer (Brookfield). The hematocrit-to-viscosity ratio (HVR) was calculated as follows: hematocrit/blood viscosity at 300 s-1. RBC adhesion to laminin (BioLamina) was assessed in 4/12 patients (3 HbSS not on RBCX, 1 HbSC) using a microfluidic device (IBIDI μ-Slide VI 0.4). Statistical analysis was performed in Graphpad Prism v9.3.0 using the Friedman test. Results Ex vivo treatment of blood of SCD patients with RCitNacQCarLKHVS showed a significant dose-dependent increase in Ohyper as measured by osmotic gradient ektacytometry (Figure 1), indicating an improvement of RBC hydration status of SCD RBCs. This was accompanied by a significant increase in mean corpuscular volume (MCV) and reduction in mean corpuscular Hb concentration (MCHC). RBCs of healthy controls showed a similar trend in Ohyper, MCV and MCHC. In addition, %DRBCs showed a significant dose-dependent decrease in both HbSS and HbSC RBCs as a result of RCitNacQCarLKHVS treatment. Oxygen gradient ektacytometry showed a significant increase in maximum deformability (EImax), but no significant change in point of sickling. The HVR did not significantly change during dose-response experiments. Median RBC adhesion to laminin decreased as a result of ex vivo treatment with RCitNacQCarLKHVS (Figure 2). Conclusion Ex vivo treatment with RCitNacQCarLKHVS demonstrated a significant dose-dependent increase in RBC hydration (Ohyper, MCV, MCHC and %DRBCs), deformability (EImax) and decreased adhesion properties in SCD RBCs. Dehydrated and dense RBCs with reduced deformability and increased adhesion are more prone to hemolysis, and associated with vaso-occlusive complications such as priapism, skin ulcers, and nephropathy. Results from this study therefore suggest benefit of EMM in modulating clinically-relevant rheological properties such as hydration state and adhesion of SCD RBCs in both SCA and HbSC. The fact that HVR did not change may represent an additional therapeutic benefit, especially for HbSC patients who have, in general, higher blood viscosity compared to HbSS patients. Moreover, it would be worthwhile to investigate if the concomitant use of select amino acid combinations with HU or other anti-sickling agents has an additional beneficial effect in SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of Reactive Species on Amino Acids-Biological Relevance in Proteins and Induced Pathologies.

This review examines the impact of reactive species RS (of oxygen ROS, nitrogen RNS and halogens RHS) on various amino acids, analyzed from a reactive point of view of how during these reactions, the molecules are hydroxylated, nitrated, or halogenated such that they can lose their capacity to form part of the proteins or peptides, and can lose their function. The reactions of the RS with several amino acids are described, and an attempt was made to review and explain the chemical mechanisms of the formation of the hydroxylated, nitrated, and halogenated derivatives. One aim of this work is to provide a theoretical analysis of the amino acids and derivatives compounds in the possible positions. Tyrosine, methionine, cysteine, and tryptophan can react with the harmful peroxynitrite or •OH and •NO2 radicals and glycine, serine, alanine, valine, arginine, lysine, tyrosine, histidine, cysteine, methionine, cystine, tryptophan, glutamine and asparagine can react with hypochlorous acid HOCl. These theoretical results may help to explain the loss of function of proteins subjected to these three types of reactive stresses. We hope that this work can help to assess the potential damage that reactive species can cause to free amino acids or the corresponding residues when they are part of peptides and proteins.

Gastrointestinal fate of phenolic compounds and amino derivatives from the cocoa shell: An in vitro and in silico approach

The objective of this study was to assess how in vitro gastrointestinal digestion influenced the bioaccessibility and potential bioavailability of phenolic compounds and methylxanthines in thecocoa shell (CS) in the form of flour (CSF) and aqueous extract (CSE). To comprehend how these phytochemicals behaved during gastrointestinal digestion, we also modeled in silico the colonic microbial biotransformation of the phenolic compounds in the CS. Different groups of phenolic compounds (mainly gallic andprotocatechuic acids, and catechin) and methylxanthines (theobromine and caffeine)could be found in the CS. Methylxanthines and phenolic compounds were released differently during gastrointestinal digestion. Whereas digestion triggered the release of hydroxybenzoic acids (67–73%) and flavan-3-ols (73–88%) during the intestinal phase, it also caused the degradation of flavonols and flavones. Besides, the release of phytochemicals was significantly influenced by the CS matrix type. Phenolic compounds were protected by the CSF matrix. Phenolic acids from CSF were more bioaccessible in the intestinal (1.2-fold, p < 0.05) and colonic (1.3-fold, p < 0.05) phases than those from the CSE. Methylxanthines were also more bioaccessible in the intestinal (1.8-fold, p < 0.01) and colonic phases (1.3-fold, p < 0.001) and bioavailable (1.8-fold, p < 0.001) in the CSF. Colonic metabolism demonstrated that the gut microbiota could biotransform non-absorbed phenolic compounds into other lower molecular weight and more bioavailable metabolites. These findings support the CS’s potential as a source of bioaccessible, bioavailable, and active phytochemicals.

Potential Plasma Metabolite Biomarkers of Diabetic Nephropathy: Untargeted Metabolomics Study.

Diabetic nephropathy (DN) is one of the specific complications of diabetes mellitus and one of the leading kidney-related disorders, often requiring renal replacement therapy. Currently, the tests commonly used for the diagnosis of DN, albuminuria (AU) and glomerular filtration rate (GFR), have limited sensitivity and specificity and can usually be noted when typical morphological changes in the kidney have already been manifested. That is why the extreme urgency of the problem of early diagnosis of this disease exists. The untargeted metabolomics analysis of blood plasma samples from 80 patients with type 1 diabetes and early and late stages of DN according to GFR was performed using direct injection mass spectrometry and bioinformatics analysis for diagnosing signatures construction. Among the dysregulated metabolites, combinations of 15 compounds, including amino acids and derivatives, monosaccharides, organic acids, and uremic toxins were selected for signatures for DN diagnosis. The selected metabolite combinations have shown high performance for diagnosing of DN, especially for the late stage (up to 99%). Despite the metabolite signature determined for the early stage of DN being characterized by a diagnostic performance of 81%, these metabolites as potential biomarkers might be useful in the evaluation of treatment of the disease, especially at early stages that may reduce the risk of kidney failure development.

Synthesis, molecular structure, conformational, and intramolecular hydrogen bond strength of ethyl 3-amino-2-butenoate and its N-Me, N-Ph, and N-Bn analogs; An experimental and theoretical study

Amino derivatives of ethyl acetoacetate like ethyl (Z)- 3-(amino)but-2-enoate (EAB), ethyl (Z)- 3-(methylamino)but-2-enoate (Me-EAB), ethyl (Z)- 3-(phenylamino)but-2-enoate (Ph-EAB), and ethyl (Z)- 3-(benzylamino)but-2-enoate (Bn-EAB) were synthesized. Their structures, conformations, and intramolecular hydrogen bonding (IHB) is characterized using computational analysis (density functional theory, DFT, methods) at the B3LYP/6-311++G(d,p) level and spectroscopic techniques)IR, UV, and NMR). All the mentioned theoretical and experimental results were compared to those of (Z)-methyl 3-aminobut-2-enoate (MAB). The vibrational spectra of EAB are fully assigned. Vibrational spectroscopy results confirmed the existence of two conformers of title molecules. DFT calculations at the B3LYP/6-311++G(d,p) level show the calculated NH bond lengths in EAB, Me-EAB, Ph-EAB, Bn-EAB, and MAB are 1.015, 1.017, 1.022, 1.018, and 1.014 Ǻ, respectively. Also, according to the natural bond orbital (NBO) results, the σN-H10↔LP(2)O7 interactions for EAB, Me-EAB, Ph-EAB, Bn-EAB, and MAB are 5.21, 6.77, 8.65, 7.18, and 5.11 kcal/mol, respectively. So, the trend in IHB strength is: Ph-EAB > Bn-EAB ∼ Me-EAB > EAB ∼ MAB, which also agrees with the mentioned experimental results. The mentioned trend also is confirmed by the LP(O7)↔σNH steric exchange interaction.

Steering bi-directional charge transfer via non-conjugated insulating polymer

Exquisite tuning of spatial charge transfer and separation has been an enduringly core issue in heterogeneous photocatalysis. Nevertheless, precise modulation of directional charge transfer to the ideal catalytically active sites remains challenging owing to rapid recombination rate of photoinduced charge carriers and sluggish charge transfer kinetics. Herein, bi-directional spatially separated electron and hole transport channels were simultaneously constructed over transition metal chalcogenides (TMCs)-based heterostructures via an efficient and facile electrostatic self-assembly strategy. Tailor-made positively charged non-conjugated polymer of branched polyethyleneimine (BPEI) and negatively charged metal nanocrystals (NCs) building blocks were controllably anchored on the TMCs substrate. We found that electrons photoexcited over TMCs substrate can migrate spontaneously, smoothly and unidirectionally to the tightly integrated neighboring metal NCs, wherein metal NCs function as Schottky-type electron-trapping reservoirs and the ultra-thin intermediate BPEI layer serves as a directional hole transport mediator, thus synergistically contributing to the significantly enhanced charge separation and prolonged charge lifetime. Benefiting from these merits, such self-assembled TMC@BPEI/metal heterostructure exhibits the markedly enhanced photoreduction catalysis toward photocatalytic hydrogen generation and anaerobic selective reduction of nitroaromatics to amino derivatives under visible light irradiation. Our work would provide inspiring idea for fine modulation of charge separation and transfer toward solar-to-chemical energy conversion.

Structure of the human heterodimeric transporter 4F2hc-LAT2 in complex with Anticalin, an alternative binding protein for applications in single-particle cryo-EM

Cryo-EM structure determination of relatively small and flexible membrane proteins at high resolution is challenging. Increasing the size and structural features by binding of high affinity proteins to the biomolecular target allows for better particle alignment and may result in structural models of higher resolution and quality. Anticalins are alternative binding proteins to antibodies, which are based on the lipocalin scaffold and show potential for theranostic applications. The human heterodimeric amino acid transporter 4F2hc-LAT2 is a membrane protein complex that mediates transport of certain amino acids and derivatives thereof across the plasma membrane. Here, we present and discuss the cryo-EM structure of human 4F2hc-LAT2 in complex with the anticalin D11vs at 3.2 Å resolution. Relative high local map resolution (2.8–3.0 Å) in the LAT2 substrate binding site together with molecular dynamics simulations indicated the presence of fixed water molecules potentially involved in shaping and stabilizing this region. Finally, the presented work expands the application portfolio of anticalins and widens the toolset of binding proteins to promote high-resolution structure solution by single-particle cryo-EM.

Intramolecular Interactions in Derivatives of Uracil Tautomers.

The influence of solvents on intramolecular interactions in 5- or 6-substituted nitro and amino derivatives of six tautomeric forms of uracil was investigated. For this purpose, the density functional theory (B97-D3/aug-cc-pVDZ) calculations were performed in ten environments (1 &gt; ε &gt; 109) using the polarizable continuum model (PCM) of solvation. The substituents were characterized by electronic (charge of the substituent active region, cSAR) and geometric parameters. Intramolecular interactions between non-covalently bonded atoms were investigated using the theory of atoms in molecules (AIM) and the non-covalent interaction index (NCI) method, which allowed discussion of possible interactions between the substituents and N/NH endocyclic as well as =O/-OH exocyclic groups. The nitro group was more electron-withdrawing in the 5 than in the 6 position, while the opposite effect was observed in the case of electron donation of the amino group. These properties of both groups were enhanced in polar solvents; the enhancement depended on the ortho interactions. Substitution or solvation did not change tautomeric preferences of uracil significantly. However, the formation of a strong NO∙∙∙HO intramolecular hydrogen bond in the 5-NO2 derivative stabilized the dienol tautomer from +17.9 (unsubstituted) to +5.4 kcal/mol (substituted, energy relative to the most stable diketo tautomer).

Microwave assisted synthesis of 2-amino-4-chloro-pyrimidine derivatives: Anticancer and computational study on potential inhibitory action against COVID-19

We report microwave synthesis of seven unique pyrimidine anchored derivatives (1–7) incorporating multifunctional amino derivatives along with their in vitro anticancer activity and their activity against COVID-19 in silico. 1–7 were characterized by different analytical and spectroscopic techniques. Cytotoxic activity of 1–7 was tested against HCT116 and MCF7 cell lines, whereby 6 exhibited highest anticancer activity on HCT116 and MCF7 with EC50 values of 89.24 ± 1.36 µM and 89.37 ± 1.17 µM, respectively.Molecular docking was performed for derivatives (1–7) on main protease for SARS-CoV-2 (PDB ID: 6LU7). Results revealed that most of the derivatives had superior or equivalent affinity for the 3CLpro, as determined by docking and binding energy scores. 6 topped the rest with highest binding energy score of −8.12 kcal/mol with inhibition constant reported as 1.11 µM. ADME, drug-likeness, and pharmacokinetics properties of 1–7 were tested using Swiss ADME tool. Toxicity analysis was done with pkCSM online server.All derivatives showed high GI absorption. Except 1 and 3, all derivatives showed blood brain barrier permeability. Most derivatives showed negative logKp values suggesting derivatives are less skin permeable and bioavailability score of all derivatives was 0.55. The toxicity analysis demonstrated that all derivatives have no skin sensitization properties. 6 and 7 showed maximum tolerated dose (Human) values of −0.03 and −0.018, respectively and absence of AMES toxicity.

Synthesis, biological evaluation, and molecular docking studies of novel diclofenac derivatives as antibacterial agents

In the recent years, interest in the synthesis of diclofenac derivatives has increased due to their exceptional biological activity. We present here the synthesis of some novel diclofenac derivatives through simple synthetic procedures, where the acylation of carbohydrazide compound 1 with chloroacetyl chloride in dioxane produced the compound 2. Chloroacetohydrazide compound 2 was further subjected to nucleophilic substitution reactions using different nucleophiles such as: hydrazine hydrate, thiosemicarbazide and p-aminobenzenesulfonamide to give the corresponding derivatives 3-5, respectively. Moreover, the reaction of the hydrazinyl compound 3 with active hydrogen species such as: ethyl acetoacetate and acetyl acetone in refluxed ethanol provided the corresponding pyrazolone derivatives 6 and 7, respectively. Furthermore, the reaction of previously reported diclofenac ester 8 with 1,2-diaminoethane gave the amino derivative 9. Finally, condensation reaction of the latter compound with benzaldehyde in dioxan furnished the corresponding Schiff's base compound 10, while its acylation with chloroacetyl chloride in dioxan produced 11. Different spectral (IR, NMR and Mass) and elemental analysis techniques were utilized to explore the structure of the synthesized compounds. All the synthesized compounds were tested for their in-vitro antibacterial activity against different strains of bacteria showing satisfactory results, and molecular docking study was performed to investigate the mode of action.

The Medicinal Functionality of Quinazolines

Quinazolines are organic compounds that are made up of two fused six-membered rings–benzene ring and pyrimidine ring. Referring to the various positions of N atoms in the cyclic ring, many other isomeric forms play a vital role in biological activities. There view article describes the main functional groups that are present in Quinazolines which are responsible for medicinal, antimicrobial, antiviral, antibacterial andanticancer actions. This review focuses on the properties of these functional groups responsible for various biological activities of Quinazolines. The heterocyclic ring structures are mainly responsible for the pharmacological effects of quinazolines. The presence of benzyl-, halo-, methoxy and amino derivatives has many anticancer, antimicrobial and antimalarial properties. The article aims to review the medicinal functionality of Quinazolines.

Comparative metabolomics of Himalayan crab apple (Malus baccata) with commercially utilized apple (Malus domestica) using UHPLC-QTOF-IMS coupled with multivariate analysis

A comprehensive UHPLC-QTOF-IMS based metabolomics investigation in skin and pulp of Malus domestica and Malus baccata was performed. M. domestica fruit parts had higher phenolic contents (25.75–43.05 mg GAE/g) as compared to M. baccata (18.10–28.37 mg GAE/g) and flavonoid content (1.34–9.59 mg RE/g) followed by promising antioxidant activity (MD_Skin DPPH 119.41 µg/mL and MB_Skin DPPH 148.24 µg/mL). Targeted metabolomics quantified higher chlorogenic acid in MD_pulp (929.54 mg/100 g) and phloridzin in MD_skin (722.54 mg/100 g). Amino acids, sugars, flavonoids, vitamins, nucleosides, quinones, fatty acids, and derivatives are among the 248 distinctive metabolites identified using non-targeted metabolomics. Multivariate data analysis, VIP projection and pathway interaction studies demonstrated the metabolic changes and differential distribution in both fruits. Using KEGG pathway enrichment analysis, the biosynthesis of flavone and flavonols is the most prevalent in both fruits. The current study found that M. baccata has a comparable metabolite distribution and should be considered for health-beneficial products.

Identification of key taste components in two aromatic rice varieties by widely targeted metabolomics in China

AbstractBackground and ObjectivesDue to the lack of comprehensive evaluation of all metabolites in rice, the metabolic reasons for taste differences are unclear. Here, two local varieties Wuyoudao 4 (WYD) (rich‐sweet flavor) and Nanjing 9108 (NJ) (delicate‐sweet flavor) were selected for ultra‐performance liquid chromatography‐tandem mass spectrometry based widely targeted metabolomic analysis.FindingsWYD and NJ were clearly separated by principal component analysis and hierarchical clustering analysis, and 231 metabolites were different between the cultivars, including 35 amino acids and derivatives, 14 saccharides and alcohols, and 12 organic acids. Among them, glucose, fructose, arabitol, and xylitol, contributed mainly to the rich‐sweet flavor of WYD rice. Leucine, phenylalanine, tryptophan, isocitric acid, and malic acid were the dominant compounds in NJ rice, and therefore, contributed primarily to the delicate‐sweet flavor.ConclusionsVital compounds of rich‐sweet for WYD, and delicate‐sweet for NJ were clear. The differential metabolites were significantly enriched in the glucosinolate biosynthesis, valine, leucine and isoleucine degradation, and 2‐oxocarboxylic acid metabolism pathways.Significance and NoveltyThis study would provide fundamental insights into the taste formation compounds and mechanism of aromatic rice.

Reshaping the Binding Pocket of the Neurotransmitter:Solute Symporter (NSS) Family Transporter SLC6A14 (ATB0,+) Selectively Reduces Access for Cationic Amino Acids and Derivatives.

SLC6A14 (ATB0,+) is unique among SLC proteins in its ability to transport 18 of the 20 proteinogenic (dipolar and cationic) amino acids and naturally occurring and synthetic analogues (including anti-viral prodrugs and nitric oxide synthase (NOS) inhibitors). SLC6A14 mediates amino acid uptake in multiple cell types where increased expression is associated with pathophysiological conditions including some cancers. Here, we investigated how a key position within the core LeuT-fold structure of SLC6A14 influences substrate specificity. Homology modelling and sequence analysis identified the transmembrane domain 3 residue V128 as equivalent to a position known to influence substrate specificity in distantly related SLC36 and SLC38 amino acid transporters. SLC6A14, with and without V128 mutations, was heterologously expressed and function determined by radiotracer solute uptake and electrophysiological measurement of transporter-associated current. Substituting the amino acid residue occupying the SLC6A14 128 position modified the binding pocket environment and selectively disrupted transport of cationic (but not dipolar) amino acids and related NOS inhibitors. By understanding the molecular basis of amino acid transporter substrate specificity we can improve knowledge of how this multi-functional transporter can be targeted and how the LeuT-fold facilitates such diversity in function among the SLC6 family and other SLC amino acid transporters.