Amino Derivatives Research Articles

Ratiometric Fluorescence Assay for Nitroreductase Activity: Locked-Flavylium Fluorophore as a NTR-Sensitive Molecular Probe.

Nitroreductases belong to a member of flavin-containing enzymes that can reduce nitroaromatic compounds to amino derivatives with NADH as an electron donor. NTR activity is known to be elevated in the cancerous environment and is considered an advantageous target in therapeutic prodrugs for the treatment of cancer. Here, we developed a ratiometric fluorescent molecule for observing NTR activity in living cells. This can provide a selective and sensitive response to NTR with a distinct increase in fluorescence ratio (FI530/FI630) as well as color changes. We also found a significant increase in NTR activity in cervical cancer HeLa and lung cancer A549 cells compared to non-cancerous NIH3T3. We proposed that this new ratiometric fluorescent molecule could potentially be used as a NTR-sensitive molecular probe in the field of cancer diagnosis and treatment development related to NTR activity.

Metabolomic and transcriptomic profiling reveals distinct nutritional properties of cassavas with different flesh colors

Cassava is a significant food security crop in several developing countries. Metabolites in cassava roots provide numerous nutrients essential for human health. Exploiting the diversity of nutritional ingredients present in cassavas is vital for improving its nutritional value. To address this problem, root metabolomes of three cassava cultivars with white-flesh, light-yellow-flesh and yellow-flesh were comprehensively measured, respectively. A total of 508 metabolites were detected in cassava roots, including 300 primary metabolites and 185 secondary metabolites. There were 22.6% to 34.1% metabolites exhibiting significant variations among the three cassava cultivars. The light-yellow-flesh cassava contained higher contents of secondary metabolites, especially flavone, phenylpropanoids and alkaloids, and lower contents of primary metabolites except lipids, alcohols, vitamins and derivatives. Compared with light-yellow-flesh cassava, the yellow-flesh cassava contained higher contents of amino acid and derivatives, but lower contents of phenylpropanoids, nucleotide and derivates. White-flesh cassava contained higher contents of primary metabolites, especially amino acid and derivatives, but lower contents of secondary metabolites except flavonoid and indole derivatives. Transcriptome analyses were parallelly performed to decipher the potential mechanisms regulating the accumulations of related metabolites. Several pathways were both enriched by differentially expressed genes and differentially accumulated metabolites, supporting that metabolisms of these metabolites were regulated at transcriptional level. These results expand the knowledge on metabolite compositions in cassava roots and provide substantial information for genetic improvement of cassavas with high nutritional values.

Transmittance of electronic effects in the fluorescein molecule: nitro and amino groups in the phthalic acid residue

This paper is aimed to estimate the transmittance of the electronic effects in the fluorescein molecule between the phthalic acid residue and the xanthene moiety. Despite the almost orthogonal orientation of the latter with respect to the rest of the molecule, some influence of substituents in this 9-aryl ring on the dissociation of the hydroxyl group of the hydroxyxanthene cannot be ruled out. In order to reveal this (possible) effect, we blocked the carboxylic group via esterification. The reason of using dimethyl sulfoxide as solvent was the high Hammett’s “rho” constant for phenolic group. The pKa values of eight methyl or ethyl esters of 3'-, 4'-, and 5'-nitro and amino fluoresceins were determined in benzoate and salicylate buffer solutions using the spectrophotometric method. For nitro derivatives, the dissociation constants of the cationic forms of the dyes were also determined in diluted p-toluenesulfonic acid. The study reveals increasing in the pKa by 0.2–0.3 units in the case of amino derivatives, while the nitro group decreases the pKas by 0.2–0.8. Also, the position of the substituent is of importance; the 5'-substituents display the least influence. In addition, the pKa values of methyl and ethyl esters of eosin (2,4,5,7-tetrabromofluorescein) were determined in order to clarify the influence of the alkyl group. The absorption maxima and molar absorptivities of the anions, as well as the pKas in DMSO coincide within the margin of errors.

Real-time monitoring of aristolochic acid I reduction process using surface-enhanced Raman Spectroscopy with DFT simulation

With the increasing number of reports on aristolochic acid I (AAI), more and more toxic and side effects have been discovered successively. The main recognized carcinogenic mechanism is that AAI is metabolized into aristololactam I (AAT) in the body by nitroreductases, ultimately forming AAT-DNA adducts that cause disease. However, the carcinogenic mechanism is still not well understood by currently reported indirect method, there has always been a great demand to develop a direct method for real-time monitoring such process. In this work, surface-enhanced Raman spectroscopy (SERS) was used for the first time to monitor the process of AAI under the action of reducing agent sodium borohydride and catalyst Raney nickel to form AAT. We first found the abundant intermediate product-amino derivative of AAI, which was never reported before by other methods. The AAT was then obtained by a one-step dehydration reaction from the amino derivative of AAI under such reduction conditions. The product of amino derivative of AAI and AAT were further verified by thin-layer chromatography, H nuclear magnetic resonance spectra, mass spectrometry, and ultra-high performance liquid chromatography. Furthermore, a density functional theory-supported in-depth vibrational characterization of AAI and AAT was performed. The monitoring of the AAI reduction process by SERS can be of great significance for further exploration of its pathogenic mechanism, prevention, and monitoring of “nephropathy” and other diseases caused by AAI.

Metabolomics Analyses of Cotyledon and Plumule Showing the Potential Domestic Selection in Lotus Breeding

Lotus (Nelumbo nucifera) seeds are widely consumed as functional food or herbal medicine, of which cotyledon (CL) is the main edible part, and lotus plumule (LP) is commonly utilized in traditional Chinese medicine. However, few studies have been conducted to investigate the chemical components of CL and LP in dry lotus seeds, not to mention the comparison between wild and domesticated varieties. In this study, a widely targeted metabolomics approach based on Ultra Performance Liquid Chromatography-electrospray ionization-Tandem mass spectrometry (UPLC-ESI-MS/MS) was utilized to analyze the metabolites in CL and LP of China Antique (“CA”, a wild variety) and Jianxuan-17 (“JX”, a popular cultivar). A total of 402 metabolites were identified, which included flavonoids (23.08% to 27.84%), amino acids and derivatives (14.18–16.57%), phenolic acids (11.49–12.63%), and lipids (9.14–10.95%). These metabolites were classified into ten clusters based on their organ or cultivar-specific characters. Most of these metabolites were more abundant in LP than in CL for both varieties, except for metabolites belonging to organic acids and lipids. The analysis of differentially accumulated metabolites (DAMs) demonstrated that more than 25% of metabolites detected in our study were DAMs in CL and LP comparing “JX” with “CA”, most of which were less abundant in “JX”, including 35 flavonoids in LP, 23 amino acids and derivatives in CL, 7 alkaloids in CL, and 10 nucleotides and derivatives in LP, whereas all of 11 differentially accumulated lipids in LP were more abundant in “JX”. Together with the fact that the seed yield of “JX” is much higher than that of “CA”, these results indicated that abundant metabolites, especially the functional secondary metabolites (mainly flavonoids and alkaloids), were lost during the process of breeding selection.

Oxatriazoles: Potential Frameworks for Energetic Compounds?

AbstractFourteen oxatriazoles have been investigated computationally as potential energetic compounds. They include the two isomeric parent compounds, their amino and nitro derivatives, four N‐oxides and four amino‐N‐oxides. Densities and solid state heats of formation were calculated for all of these compounds, and used to determine their detonation velocities and detonation pressures by means of the Kamlet‐Jacobs equations. Four of the compounds, all N‐oxides, surpass or essentially equal Klapötke's criteria for detonation velocity and detonation pressure. Three other N‐oxides meet just the detonation velocity criterion. Impact sensitivity was addressed in terms of three factors that are known to affect it: the free space per molecule in the crystal lattice, the electrostatic potential on the molecular surface, and the detonation heat release of the compound. Three of the N‐oxides with the highest detonation velocities and detonation pressures have undesirably large heats of detonation, a warning of possible impact sensitivity. However 5‐amino‐1,2,3,4‐oxatriazole‐3‐oxide combines good detonation properties with a moderate heat release; its free space per molecule in the crystal lattice and molecular surface electrostatic potential are also consistent with low sensitivity. Overall, we believe that the results of this work should encourage further investigation of oxatriazole derivatives as energetic compounds.

Development of bio-based benzoxazines coated melamine foam for oil-water separation

Mono and di-functional benzoxazines were developed based on both sustainable bio-based cardanol and less hazardous synthetic bisphenol-F using mono and di amino derivatives with paraformaldehyde under appropriate experimental conditions. The molecular structure of the developed benzoxazines was confirmed using FTIR and 1HNMR spectra. The ring opening polymerization of developed benzoxazines was studied using differential scanning calorimetry to ascertain their cure behaviour. The hydrophophic and oleophhilic behaviour of benzoxazines coated melamine foam developed in the present work were ascertained from the values of water contact angle determined using goniometer. The optimum concentration required to transform hydrophilic melamine foam in to hydrophobic/oleophilic nature was studied using varying weight percentage amount of benzoxazines as coating material. Based on the results of water contact angle obtained for 25 wt%, 50 wt%, 75 wt% and 100 wt% of benzoxazine coated on melamine foam, it was ascertained that 50 wt% of benzoxazine was required to obtain maximum water contact angle. The values of water contact angle obtained for 50 wt% of C-a, C-l, C-s, C-h, C-i, BF-l and BF-s are 150˚,153˚,155˚,153˚,158˚,150˚and152˚respectively. It was also noticed that, among the different benzoxazines coated melamine foam, 50 wt% C-i possesses the highest value of water contact angle of 158˚. The oil (engine oil, mineral oil and soybean oil) absorption capacity of different polybenzoxazines coated melamine foam was obtained in the range between 85 and 95 times based on the weight of melamine foam. It is concluded from the results obtained, the materials developed in the present work has great utility in the field of oil/water separation and environmental pollution control.

Synthesis and evaluation of 2,3,4,9-tetrahydro-1H-carbazole derivatives as selective acetylcholinesterase inhibitors: Potential anti-Alzheimer’s agents

Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys memory and cognition skills. Dysfunction of acetylcholine containing neurons in the brain contributes substantially to the cognitive decline observed in Alzheimer's disease. Hence, our focus is to synthesize cholinesterase inhibitors. A series (22 compounds) of 6- and 9-substituted derivatives of 2,3,4,9-tetrahydro-1H-carbazole have been prepared and in vitro evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition by Ellman’s method. By comparing selectivity with standard drug donepezil, amino derivative 3, methylamino derivative 4 and butyl nitro derivative 17 have been found to be selective AChE inhibitors. Borsche-Drechsel cyclization reaction has been carried out to synthesize 2,3,4,9-tetrahydrocarbazole ring followed by nitration, reduction and derivative synthesis.

One‐potandtwo‐potmethods for chalcone derived pyrimidines synthesis and applications

AbstractChalcone‐derived pyrimidine is a well‐known heterocyclic compound that is commonly present in ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) bio‐isosteres. Pyrimidine derivatives are effective in both the electronic industry and drug industries. This review highlights the synthesis of pyrimidines, namely mono‐pyrimidine, bis‐pyrimidine, fused pyrimidine, symmetric, and asymmetric pyrimidine via one‐pot and two‐pot methods. The one‐pot method is the direct reaction of amino derivatives with aldehydes and acetophenones, whereas the two‐pot method is frequently reported for the synthesis of chalcone before the cyclization to a pyrimidine. This review is important in organic synthesis, particularly in the heterocyclic field, regarding pyrimidines and their significance in therapeutic and electronic industries.

Flux redistribution of central carbon metabolism for efficient production of l-tryptophan in Escherichia coli.

Microbial production of l-tryptophan (l-trp) has received considerable attention because of its diverse applications in food additives and pharmaceuticals. Overexpression of rate-limiting enzymes and blockage of competing pathways can effectively promote microbial production of l-trp. However, the biosynthetic process remains suboptimal due to imbalanced flux distribution between central carbon and tryptophan metabolism, presenting a major challenge to further improvement of l-trp yield. In this study, we redistributed central carbon metabolism to improve phosphoenolpyruvate (PEP) and erythrose-4-phosphate (E4P) pools in an l-trp producing strain of Escherichia coli for efficient l-trp synthesis. To do this, a phosphoketolase from Bifidobacterium adolescentis was introduced to strengthen E4P formation, and the l-trp titer and yield increased to 10.8 g/L and 0.148 g/g glucose, respectively. Next, the phosphotransferase system was substituted with PEP-independent glucose transport, meditated by a glucose facilitator from Zymomonas mobilis and native glucokinase. This modification improved l-trp yield to 0.164 g/g glucose, concomitant with 58% and 40% decreases of acetate and lactate accumulation, respectively. Then, to channel more central carbon flux to the tryptophan biosynthetic pathway, several metabolic engineering strategies were applied to rewire the PEP-pyruvate-oxaloacetate node. Finally, the constructed strain SX11 produced 41.7 g/L l-trp with an overall yield of 0.227 g/g glucose after 40 h fed-batch fermentation in 5-L bioreactor. This is the highest overall yield of l-trp ever reported from a rationally engineered strain. Our results suggest the flux redistribution of central carbon metabolism to maintain sufficient supply of PEP and E4P is a promising strategy for efficient l-trp biosynthesis, and this strategy would likely also increase the production of other aromatic amino acids and derivatives.

Synthesis of Some New Folic Acid-Based Heterocycles of Anticipated Biological Activity

To date, no fused heterocycles have been formed on folic acid molecules; for this reason, and others, our target is to synthesize new derivatives of folic acid as isolated or fused systems. Folic acid 1 reacted with ethyl pyruvate, triethyl orthoformate, ethyl chloroformate, thioformic acid hydrazide, and aldehydes to give new derivatives of folic acid 2–6a,b. Moreover, It reacted with benzylidene malononitrile, acetylacetone, ninhydrin, ethyl acetoacetate, ethyl cyanoacetate, and ethyl chloroacetate to give the pteridine fused systems 10–15, respectively. Ethoxycarbonylamino derivate 5 reacted with some nucleophiles containing the NH2 group, such as aminoguanidinium hydrocarbonate, hydrazine hydrate, glycine, thioformic acid hydrazide, and sulfa drugs in different conditions to give the urea derivatives 16–20a,b. Compound 4 reacted with the same nucleophiles to give the methylidene amino derivatives 21–24a,b. The fused compound 10 reacted with thioglycolic acid carbon disulfide, malononitrile, and formamide to give the four cyclic fused systems 25–30, respectively. The biological activity of some synthesized showed moderate effect against bacteria, but no effect shown towards fungi.

A facile and green synthesis of CuO/NiO nanoparticles and their removal activity of toxic nitro compounds in aqueous medium

In this present work, we report the green synthesis of mixed bimetal oxides (CuO/NiO) for the efficient reduction of toxic nitrophenols (NP, DNP and TNP) in aqueous medium. The CuO/NiO NPs were synthesized by green hydrothermal method combined calcination process. The physiochemical properties of the synthesized CuO/NiO NPs were systematically characterized by using XRD, XPS, FTIR, SEM, and HR-TEM techniques. The calcinated CuO/NiO NPs XRD pattern and SEM morphology show the high crystalline nature than the non-calcinated. Whereas, the XPS and FTIR results confirmed the formation of the metal oxide bonding and the interaction of the bimetals. The HR-TEM images showed the spherical crystals with average particle size about 25 nm. In addition, the SAED pattern confirmed the polycrystalline nature of CuO/NiO NPs. The catalytic reduction of nitro compounds to amino derivative was studied with reducing agent (NaBH4). The CuO/NiO NPs showed the high catalytic activity and completed the reduction reaction of NP, DNP and TNP with in 2, 5 and 10 min respectively. In addition, CuO/NiO NPS exhibited the excellent kinetic rate constant k value about 1.519, 0.5102, 0.4601 min−1 for NP, DNP and TNP respectively. Furthermore, the conversion product aminophenol was observed for these three nitro compounds. The proposed CuO/NiO NPs showed excellent crystal stability after the nitrophenol reduction reactions. An inexpensive CuO/NiO NPs is a promising catalysts for reduction of toxic nitro compounds to useful products in aqueous or non-aqueous medium.

Targeted metabolomics reveals dynamic portrayal of amino acids and derivatives in triple-negative breast cancer cells and culture media.

Triple-negative breast cancer (TNBC) is well-known for its metastatic aggressiveness and poor survival prognosis, accounting for nearly a quarter of cases in breast cancer. We performed intra- and extra-cellular profiling of 40 amino acids and derivatives on three cell lines and their culture media, including TNBC, non-TNBC and normal breast epithelial cells, using HILIC-MS/MS. Characteristic metabolic alteration of amino acids and derivatives was observed in TNBC cells, compared to non-TNBC cells, especially in correlated intra- and extra-cellular metabolic pathways. Intra-cellularly, quantified glutamic acid, β-alanine, aspartic acid, glutathione, N-acetyl-serine and N-acetyl-methionine were most significantly increased (>2-fold, p < 0.01 and VIP > 1) in TNBC cells. Extra-cellularly, significantly increased uptake of glutamine, serine, β-alanine, and lysine and elevated excretion of glutamic acid and l-cysteine-glutathione (p < 0.01 and VIP > 1) were observed by TNBC cells from or to their cell culture media. This study depicted a novel dynamic portrayal of metabolic dysregulation between TNBC and non-TNBC cells, correlated in both intra- and extra-cellular amino acid profiles. Quantification of these distinctive metabolites of TNBC cells might offer advanced understanding and new treatment targets for TNBC.

Plasma levels of amino acids and derivatives in retinopathy of prematurity.

Background: Retinopathy of prematurity (ROP) is a retinal disease that causes blindness in premature infants. This study aimed to reveal the changes in amino acids and derivatives in the plasma of ROP patients compared with premature infants without ROP.Methods: Metabolomics targeting amino acids and their derivatives was conducted to assess their plasma levels in ROP patients (n=58) and premature infants without ROP (n=25), and KEGG pathway analysis was used to identify the involved pathways.Results: Among the 31 assessed metabolites, the levels of 4 amino acids were significantly altered in the ROP group. Creatinine was downregulated in the plasma of the ROP patients, while the levels of citrulline, arginine, and aminoadipic acid were upregulated in the ROP group. Significant correlations were identified between the ROP stage and plasma levels of citrulline, creatinine, and aminoadipic acid. The involved pathways included biosynthesis of amino acids, arginine and proline metabolism, and arginine biosynthesis.Conclusion: The plasma levels of citrulline, creatinine, arginine, and aminoadipic acid were significantly changed in ROP patients. These metabolites could be considered potential biomarkers of ROP, and their related metabolic pathways might be involved in ROP pathogenesis.

New cyclic and spirocyclic aminosilanes

AbstractNew cyclic and spirocyclic aminosilanes were synthesised using ethylenediamine, 2-aminobenzylamine, 1,8-diaminonaphthalene, o-phenylenediamine, andtrans-cyclohexane-1,2-diamine as starting material. These diamines were converted into aminosilanes using silicon tetrachloride and dimethyldichlorosilane directly and via theN,N’-bis(trimethylsilylated) amino derivatives. 15 new compounds of the type (diamino)(SiMe3)2, (diamino)2Si, (diamino)SiMe2, and (diamino)SiCl2have been prepared. The formation of two cyclotrisilazane derivatives was observed starting from (N,N’-2-aminobenzylamino)dichlorosilane by trimerisation. All synthesised compounds have been characterised with NMR-, Raman-, or IR-spectroscopy, mass-spectrometry, and boiling or melting point. Single-crystal X-ray structure analyses of several derivatives have been performed.The degree of substitution with trimethylsilyl groups in the final compounds depends on the ring size of the spirocycles. It was shown with quantum chemical calculations on the M062X/6-31G(d) level that trimethylsilyl groups have a stabilising effect on 5-membered ring systems and a destabilising effect on 6-membered rings in these compounds.

Organocatalytic enantioselective synthesis of β-amino sulfonic acid derivatives.

An unprecedented enantioselective conjugate addition reaction of sodium bisulfite to various nitrostyrenes occurred upon the influence of a bifunctional amino-thiourea organocatalyst; a strategy that opens a straightforward route to unprotected chiral taurine derivatives thanks to the reduction of the obtained β-nitroethanesulfonic acids into the corresponding amino derivatives.

Comparative Metabolomics Analysis between Red- and White-Flowered Common Buckwheat Cultivars

Common buckwheat (Fagopyrum esculentum), a specialty crop in southwest China, is not only used as a supplement to primary grain crops but also to produce beverages, such as tea and wine. To fully exploit the products made from common buckwheat flower, ultra-performance liquid chromatography–electrospray ionization– tandem mass spectrometry (UPLC–ESI–MS/MS) was conducted to analyze the metabolites in red- (‘Guihong 2’) and white-flowered (‘Fengtian 1’) buckwheat cultivars. A total of 784 metabolites were identified of which flavonoids were the largest group with 191 components, followed by organic acids and derivatives (126), and amino acids and derivatives (95). Besides, dozens of phenylpropanoids, nucleotides and derivates, lipids, alkaloids as well as several kinds of indole derivatives and sterides were detected. Among these rich varieties of metabolites, 24 metabolites were only detected in the red flower that mainly included 8 anthocyanins and 6 flavones, while 22 metabolites were only detected in the white flower, which mainly contained 5 lipids, 5 flavonoids, and 5 organic acids and derivatives. Our results enrich the metabolites’ information of buckwheat and may be helpful for the exploitation of products from common buckwheat flowers.

Mono- and dialdehyde of trehalose: new synthons to prepare trehalose bio-conjugates.

Trehalose, a non-reducing disaccharide of glucose, is a natural bioactive and non-toxic sugar. It is found in many organisms that synthesise it when their cells are exposed to stress conditions. While not produced by mammalian cells, this disaccharide and also some of its derivatives have been shown to have a number of interesting properties that indicate their importance in the treatment of certain human diseases. Differentiating the two glucosyl moieties in the trehalose molecule has often been a synthetic challenge. We report here an easy way to obtain the monoaldehyde of trehalose, as well as the relevant symmetrical dialdehyde. The reactivity of the aldehyde functionalities involved in the molecular structure of these synthons allows the easy preparation of the corresponding amino or carboxy derivatives of trehalose, as well the synthesis of some new trehalose conjugates useful for diagnostic or therapeutic purposes.

Targeted metabolomics reveals dynamic changes during the manufacturing process of Yuhua tea, a stir-fried green tea

The chemical composition of Yuhua tea is in a state of constant change during tea processing. However, the dynamic changes in this complex metabolic process remain unclear. Therefore, we detected the changes of compounds in the five stages of processing of Yuhua tea, and carried out metabolomic analysis based on UPLC–MS. In total, 898 metabolites were detected in the five different stages. In the spreading and fixation processes, the differences in metabolites were the most significant, with 127 and 150 metabolites, respectively, undergoing significant changes. During the spreading period, the levels of amino acids and their derivatives, as well as flavonoids, increased sharply, and most continued to increase or stabilized after spreading. In addition, only 26 and 95 metabolites changed significantly during the rolling and drying processes, respectively. Orthogonal projections to latent structures-discriminant analysis showed that the metabolomics of tea changed significantly during the manufacturing process, especially amino acids and derivatives, flavonoids and lipids. This study provides a comprehensive overview of the metabolic changes during the processing of stir-fried green tea, which has potential significance for quality control and flavor improvement of tea.

IMIDAZOANNELATED IMIDAZOLES: METHODS OF SYNTHESIS AND PRACTICAL APPLICATION

In recent decades, the chemistry of imidazoles, which are most likely due to their strong biological potential and practical application, has attracted more and more attention from scientists. The structural fragment of partially hydrogenated imidazoimidazole is an integral part of azamacrocycle precursors such as 1,4,7,10-tetraazacyclododecane and 1,4,7-triazacyclononane, important macrocycles for chelated compounds. The latter, being often paramagnetic materials, are used as contrast agents in magnetic resonance imaging (MRI), as sensitive MRI probes, are used in positron emission tomography (PET), as well as in radioimmunotherapy (RIT). Along with these uses of saturated imidazoimidazole derivatives, they have also been used as ligands in immobilized metal affinity chromatography (IMAC), the most universal method of protein purification. Analysis of the literature has shown that intermolecular cyclocondensations of amino derivatives with a nitrile moiety, intramolecular cyclocondensations of imidazole derivatives and metal-catalytic synthesis are most often used for the synthesis of imidazo[1,2-a]imidazoles. The article provides a comprehensive generalization of the known methods of obtaining imidazoimidazoles, reveals their practical application for both chemistry and medicine.