Acetyl Derivatives Research Articles

Cellular internalization mechanism of novel Raman probes designed for plant cells.

Diphenylacetylene derivatives containing different polymeric components, poly(l-lysine) (pLys) or tetra(ethylene glycol) (TEG) were designed as novel Raman imaging probes with high Raman sensitivity and low cytotoxicity in living plant cells. The pLys-conjugated probe is internalized via an endocytosis-dependent pathway, whereas TEG-conjugated probe most likely induces direct penetration into the plant cells.

Mechanical, Thermal Properties and Hirshfeld Surface Analysis of N-Acetylglycine Single Crystal

Mechanical properties of some amino acid based derivatives plays a versatile role in the device fabrication due to its mechanical strength. One such acetyl derivative of glycine named N-acetylglycine has been taken in the present study for investigation. Hardness analysis has been carried out on the grown crystal with various loads and it was observed that Vicker’s hardness number (Hv) varied for different loads. The work hardening coefficient is calculated to be 1.628 which confirms that the grown crystal comes under moderately hard material category. Other mechanical parameters like minimum load indentation (W), materials constant (k1), load dependent constant (A1) and elastic stiffness constant (C11) have also been calculated. The thermal analysis has also been carried and it reveals that the complete weight loss of N-acetylglycine starts from 208.60 ºC and ends at 281.58 ºC. The corresponding DTA peak is observed at 217.97 ºC which is the melting point of the sample. As expected, there is no phase transition till the material melts and this enhances the temperature range for the utility of the crystal. Kinetic and thermodynamic parameters have been calculated. All the results obtained from hardness as well as thermal measurement confirm the material may be suitable for electro-optic device applications. Further, the 3D Hirshfeld surface analysis and 2D fingerprint maps gives deep insight into the intermolecular interactions between the compound.

Synthesis, Characterization and Antimicrobial Activity of N-2-(4-Chlorophenyl)acetyl Derivatives of (S)-Amino Acids

This paper reports the synthesis, characterization and antibacterial activity of N-2-(4-chlorophenyl)acetyl derivatives of various (S)-amino acids such as (S)-alanine, (S)-phenylalanine, (S)-leucine, (S)-methionine, (S)-proline and (S)-tryptophane. These compounds have been successfully synthesized and their structures were confirmed by 1H NMR and 13C NMR and FT-IR spectroscopy. The antimicrobial activity of these six (S)-amino acids derivatives have been evaluated by the agar well diffusion method against pathogens both Gram-positive (S. aureus) and Gram-negative (K. aerogenes, E. coli and P. desmolyticumas) bacteria and fungi (A. flavus and C. albicans). All these compounds have shown mild to moderate antimicrobial activity.

Glycerol Acetylation Mediated by Thermally Hydrolysed Biosolids-Based Material

Crude glycerol is the main by-product of many renewable diesel production platforms. However, the process of refining glycerol from this crude by-product stream is very expensive, and thus does not currently compete with alternative processes. The acetylation of glycerol provides an intriguing strategy to recover value-added products that are employable as fuel additives. In this work, the conversion of glycerol to acetyl derivatives was facilitated by a heterogeneous catalyst generated from the thermal hydrolysis of biosolids obtained from a municipal wastewater treatment facility. The reaction was studied using several conditions including temperature, catalyst loading, acetic acid:glycerol molar ratio, and reaction time. The data demonstrate the potential for using two distinct by-product streams to generate fuel additives that can help improve the process economics of renewable diesel production.

Synthesis, Reactions and Antioxidant Activity of 5-(3', 4'-dihydroxy-tetrahydrofuran-2'-yl)-2-methyl-3-carbohydrazide

In this manuscript, we describe the synthesis of the carbohydrazide 2. Acid-catalyzed condensation with several carbonyl compounds to afford the corresponding carbohydrazide derivatives 3-12. Their acetylation afforded the corresponding acetyl derivatives 13-22. Oxidative cyclization of O-acetyl derivatives 19-22 afforded the corresponding 1,3,4-oxadiazole derivatives 23-26. On the other hand, condensation of the dicarbonyl compound 27 with several aroylhydrazines to give the corresponding bisaroylhydrazones 28-32 cyclization of 28-31 afforded 1,3,4-oxadiazoles 33-36. The structures of the prepared compounds were confirmed by 1HNMR and Mass Spectra. The mechanism of the formation of the products was discussed. Furthermore, the antioxidant activities of some of the prepared compounds were examined.

Anticancer and molecular docking studies of some new pyrazole-1-carbothioamide nucleosides

Eight pyrazole-1-carbothioamide nucleosides were synthesized through conensation of 3-(4-aminophenyl)-pyrazole-1-carbothioamide derivative 2 with four aldoses (arabinose, mannose, glucose and galactose) and acetylation of the produced nucleosides 3a-d with acetic anhydride in pyridine at room temperature to give their corresponding acetyl derivatives 4a-d. Their chemical structures were confirmed by spectroscopic and elemental analysis. The antiproliferative activity was screened against various human cancer cell lines (MCF-7, HepG2 and HCT-116) in vitro; compound 4b showed a significant IC50 values (8.5±0.72 for MCF-7, 9.4±0.84 for HepG2 and 11.7±0.89 µg/ml for HCT-116) which were close to the reference drug 5-fluorouracil (5-FU). Molecular docking study was utilized to illustrate the ability of the more active compounds 3b and 4b to inhibit thymidylate synthase and compare the results with an antimetabolite drug used in cancer chemotherapy "Raltitrexed".

Nickel Nanoparticle-catalyzed Carboxylation of Unsaturated Hydrocarbon with CO2 Using Sulfur-modified Au-supported Nickel Material

A hydrocarboxylation reaction of alkyne or styrene derivatives with CO2 proceeded smoothly by using an air-stable nano-sized nickel catalyst supported on sulfur-modified gold (SANi), giving functio...

Inhibition of the pro-inflammatory mediators in rat neutrophils by shanzhiside methyl ester and its acetyl derivative isolated from Barleria prionitis.

The aerial parts of Barleria prionitis Linn. (BP) (Acanthaceae) plant has long been used to treat inflammatory disorders such as toothache, swellings, arthritis and gout. The purpose of this study was to evaluate the effects of shanzhiside methyl ester (SME), 8-O-acetyl shanzhiside methyl ester (ASME) and iridoid glycosides rich monoterpenoidal fraction (IFBp), isolated from the aerial part of BP, on the pro-inflammatory mediators in stimulated rat neutrophils. Rat neutrophils were incubated with or without test drugs. The influence of laboratory isolated and identified SME, ASME and IFBp on the production and release of pro-inflammatory mediators i.e. myeloperoxidase (MPO), elastase, matrix metalloproteinase-9 (MMP-9), interleukin 8 (IL-8), tumor necrosis factor alpha (TNF-α) and leukotriene B4 (LTB4) was evaluated in the formyl-met-leu-phenylalanine (f-MLP) and lipopolysaccharide (LPS) stimulated rat neutrophils using enzyme-linked immunosorbent assay (ELISA) methods. IFBp was also standardized with the high performance thin layer chromatography by simultaneous determination of SME and ASME marker compounds. SME, ASME and IFBp displayed concentration-dependent inhibitory effects on the MPO, elastase and MMP-9 enzymes release, and IL-8, TNF-α and LTB4 cytokines production in the f-MLP and LPS stimulated rat neutrophils. The content of SME and ASME was found to be 17.32 ± 1.98 and 11.30 ± 1.06% w/w, respectively, in IFBp by HPTLC method. Altogether, the present results suggest that the iridoidal glycosides of BP may be considered as therapeutic strategy against neutrophil-mediated inflammatory diseases. Developed and validated HPTLC method for the standardization of IFBp of BP can be used as a quality control tool for the routine qualitative and quantitative analysis of Barleria species containing SME and/or ASME.

Synthesis of E,E-4-(6-(N-hydroxyethyl(N-ethyl)-aminostyrylquinoxalin-2-yl)vinyl)-2-dicyanomethylene-3-cyano-2,5-dihydrofurans

Nonlinear-optical chromophores with N-hydroxyethyl-N-ethylaniline donor, tricyanofuran acceptor moieties and 3,7-divinylquinoxaline π-bridge have been synthesized. The acetyl derivatives of these chromophores exhibit an intense charge transfer band in the visible region of spectrum and a large positive and negative solvatochromism in different solvents.

Change in serum polyamine metabolome pattern after bariatric surgery in obese patients with metabolic syndrome.

Recent works have reported that bariatric surgery has remarkable effects on the metabolome, which might be potentially associated to the metabolic improvement of this procedure in patients with obesity. Serum polyamines, metabolites derived from amino acid metabolism, have been recently related to the metabolic status in obese individuals. However, the impact of bariatric surgery on the circulating levels of polyamines remains elusive. To evaluate the effect of bariatric surgery on serum polyamine levels and to evaluate the association of changes in these molecules with metabolic improvement in patients with morbid obesity. Virgen de la Victoria University Hospital, Malaga, Spain. This study included 32 morbidly obese patients (weight index ≥40 kg/m2) with metabolic syndrome, who underwent sleeve gastrectomy. Serum levels of polyamines (putrescine, spermidine, and spermine), acetylpolyamines, and polyamine-related amino acids (arginine and ornithine) were assessed at baseline and 6 months after bariatric surgery, and were analyzed in an ultraperformance liquid chromatography-mass spectrometry platform. Our metabolomic analysis revealed a significant rise in several metabolites related to the polyamine metabolism, such as putrescine and acetyl derivatives of spermidine and spermine in serum samples from morbidly obese patients after bariatric surgery. Changes in serum levels of both putrescine and acetylputrescine were associated to the resolution of metabolic syndrome after surgery. Our study indicates that bariatric surgery affects the serum polyamine pattern and the resolution of metabolic syndrome after bariatric surgery is associated to specific changes in the serum polyamine metabolome.

Synthesis and Antimicrobial and Antifungal Activity of Resin Acid Acetylene Derivatives

A series of diterpenes that contain the morpholine, pyrrolidine, benzyl, nitrophenyl, and 1,2,3-tetrazole heterocyclic fragments have been synthesized from acetylene derivatives of abietic, 7-formylabietic, dehydroabietic, maleopimaric, and dihydroquinopimaric acids. The antibacterial activity of the synthesized compounds against microorganisms and pathogenic fungi has been studied, and the primary assessment of their cytotoxicity and hemolytic activity has have been carried out. It has been found that the acetylene derivatives of abietic and dehydroabietic acids that contain the pyrrolidine substituent can effectively inhibit the growth of fungi Candida albicans and Cryptococcus neoformans, and their low hemolytic ability has been shown.

Synthesis of Macrocyclic Ttipeptidopyridine Schiff Base Candidates

In the current study, a series of macrocyclic tripeptide Schiff bases 2–6 were synthesized by using macrocyclic tripeptide hydrazide 1 as starting material. Treatment of hydrazide 1 with active carbonyl cycloalkanones gave cycloalkanone hydrazines 2a–2d. Also, condensation of 1 with aromatic and heterocyclic aldehydes, or aromatic and heterocyclic acetyl derivatives afforded the corresponding Schiff base candidates 3a–3e, 4a–4c, 5a–5c, and 6a–6c, respectively.

DESIGN, SYNTHESIS AND STRUCTURAL ELUCIDATION OF ARYLOXYAMINOACETYLENIC DERIVATIVES AS ANTIDEPRESSANT ACTIVITY

Depression is the most common illness that affects a large number of individuals in all countries. It is believed that decreased levels of neurotransmitters such as serotonin, norepinephrine and dopamine are the main cause of depression. Selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (SNRIs), their mechanism is to increase the amount of neurotransmitters in the CNS. Design, synthesis and molecular docking of novel compounds namely amino acetylenic derivatives of aryloxy as isostere for aryloxypropylamine. The reaction of 7-methoxy-2-naphthol with propargylbromide generated 7-methoxy-2-(prop-2-yn-1-yloxy) naphthalene (ZR-1). ZR-1 was subjected to Mannich reaction yielded the derivatives of aryloxybutynylamines (ZR-2 to ZR-7). The Mp, FTIR, 1H-NMR, C13-NMR, DSC, elemental analysis and HPLC were consistent with the assigned structures. The molecular docking results obtained for aminoacetylenic compounds showed that the new novel 7-methoxy-2- {[4- (piperidine) but-2-yn-1-yl]oxy}-naphthalene (ZR-4) provide effective π overlap with binding sites of SERT protein by ionic, hydrogen bonding and overlap of aryl and cyclic amine moieties with the amino acids of transporter protein, which produce the binding energy (-109,69 kcal/mol) for ZR-4 relative to paroxetine (-114.18 kcal/mol), that may lead to promising drug in the treatment of depression.

Does the molecular mobility and flexibility of the saccharide ring affect the glass-forming ability of naproxen in binary mixtures?

In this paper, we studied the impact of saccharides having a similar backbone but differing in the degree of freedom, local molecular mobility, flexibility of the ring and intermolecular interactions on the glass-forming ability (GFA) of naproxen (NAP) in binary mixtures. For this purpose, a series of methyl and acetyl derivatives of glucose (GLS) and anhydroglucose (anhGLS), as well as neat anhGLS have been used to produce homogeneous solid dispersions (SDs) of varying molar concentration of examined active pharmaceutical ingredient (API). Systematic measurements with the use of Differential Scanning Calorimetry (DSC) and Broadband Dielectric Spectroscopy (BDS) enabled us to determine the phase transitions, homogeneity and molecular mobility of the investigated binary mixtures as well as the impact of excipient on the crystallization tendency of NAP. It turned out that acetylated glucose (acGLS), one of the most mobile and flexible saccharides of all examined herein materials, is the best excipient enhancing the GFA of studied API. Although, it should be noted that upon storage at room temperature, we observed the recrystallization of NAP from binary mixtures. Interestingly, API always crystallized to the initial polymorphic form, as shown by X-ray diffraction (XRD) investigations. Finally, since additional measurements with the use of Fourier Transform Infrared (FTIR) Spectroscopy clearly indicated that there are no significant differences in the intermolecular interactions in the systems composed of NAP and all examined saccharides, one can postulate that the mobility and ring flexibility of the matrix have, , the most important impact on the crystallization tendency of NAP upon cooling. Consequently, it seems that in some cases, more mobile/flexible matrices can be a much better choice to enhance the glass-forming ability of studied pharmaceutical.

Synthesis and Cytotoxic Activity of New 1,3,4-Thiadiazole Thioglycosides and 1,2,3-Triazolyl-1,3,4-Thiadiazole N-glycosides.

New 1,3,4-thiadiazole thioglycosides linked to substituted arylidine systems were synthesized via glycosylation of the prepared 1,3,4-thiadiazole thiol compounds. Click strategy was also used for the synthesis of new 1,3,4-thiadiazole and 1,2,3-triazole hybrid glycosides by reaction of the acetylenic derivatives with different glycosyl azids followed by deacetylation process. The cytotoxic activities of the prepared compounds were studied against HCT-116 (human colorectal carcinoma) and MCF-7 (human breast adenocarcinoma) cell lines using the MTT assay. The results showed that the key thiadiazolethione compounds 2 and 3, the triazole glycosides linked to p-methoxyarylidine derivatives 14 and 15 in addition to the free hydroxyl glycoside 20 were found potent in activity comparable to the reference drug doxorubicin against MCF-7 human cancer cells. The acetylenic derivative 2 and glycoside 20 were also found highly active against HCT-116 cell lines.

Can discrepancies between Fusarium graminearum trichothecene genotype and chemotype be explained by the influence of temperature in the relative production of 3-ADON and 15-ADON?

Wheat is one of the most important crops in Argentina and worldwide. One of the major diseases affecting the crop is the Fusarium Head Blight (FHB). It is an endemic disease caused mainly by Fusarium graminearum, the most common agent of FHB around the world. The infection is strongly influenced by environmental parameters and occurs mostly when there are favourable conditions of moisture and temperature during wheat anthesis or flowering. This destructive disease affects wheat, barley and other small grains and has the capability of destroying crops, causing great economic losses due to reduced grain quality, and the accumulation of significant levels of mycotoxins such as trichothecenes. The aim of this study was to evaluate the influence of temperature on mycotoxin biosynthesis, on three strains of F. graminearum of 15-ADON genotype and one of 3-ADON genotype, with different capacity of synthesizing DON, 3-ADON and 15-ADON. Trichothecene production of the strains at different temperatures (5, 10, 15, 20, 25, 30 and 35 °C) was evaluated after 7, 14, 21, 28 and 35 d of incubation. The optimum temperature to produce DON and 3-ADON was between 25 and 30 °C, but the maximum production of 15-ADON occurred at a lower temperature (10 °C) for all the strains. Conversely, the minimum production of DON and 3-ADON was recorded between 5 and 10 °C and of 15-ADON between 30 and 35 °C. A possible explanation for the similar accumulation of both acetyl derivatives by strains of different chemotype and genotypes could be that the acetyl derivatives biosynthesis is regulated by temperature.

DSC studies on the interaction of lipophilic cytarabine prodrugs with DMPC multilamellar vesicles

Cytarabine (1-β-d-arabinofuranosylcytosine, Ara-C), a pyrimidine nucleoside analogue, is used for the treatment of both acute and chronic myeloblastic leukemias and non-Hodgkin lymphoma. It has a very short plasma half-life and a very low oral bioavailability. To overcome these disadvantages, much effort has been focused on the design of cytarabine prodrugs. In this study, we have synthesized four different cytarabine prodrugs in order to increase the drug lipophilicity and the affinity of the prodrugs toward the biological membranes, as well as the lipophilic carriers. Differential scanning calorimetry was used to study the interaction of cytarabine and its prodrugs with multilamellar vesicles (MLVs) made of dimyristoylphosphatidylcholine (DMPC) and used as a model of biomembranes as well as a lipophilic carrier. The results showed that the 4-N-acetyl-2′,3′-5′-acetyl derivative and the prodrug with short chain fatty acids do not have a significant affinity with MLVs, whereas the prodrugs with long chain fatty acids have a stronger affinity with the MLVs with respect to cytarabine. The entity of the affinity depends on the fatty acids length. The increased affinity could be due to the fatty acid moieties which allow the molecule to insert among the phospholipid molecules. These results provide information on the interaction of these prodrugs with biomembranes and could be useful to design liposomes as carriers for the prodrugs.

Palladium-Catalyzed Coupling of Terminal Alkynes with Benzyl Ammonium Salts.

A highly efficient palladium-catalyzed Sonogashira coupling of benzylic ammonium salts with terminal alkynes is developed. This strategy provides a facile access to a series of internal alkyne derivatives in moderate to excellent yields via C-N bond cleavage and C(sp3)-C(sp) bond formation. The broad substrate scope and high functional group tolerance make this reaction attractive for organic synthesis.

ROS Inhibitory Activity and Cytotoxicity Evaluation of Benzoyl, Acetyl, Alkyl Ester, and Sulfonate Ester Substituted Coumarin Derivatives.

A number of non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, indomethacin, ibuprofen, flufenamic acid, and phenylbutazone are being clinically used to treat inflammatory disorders. These NSAIDs are associated with serious side effects such as gastric ulceration, nephrotoxicity, and bleeding. Therefore, the identification of potent and safe therapy for inflammatory disorders is still of great interest to the medicinal chemist. A series of varyingly substituted benzoyl, acetyl, alkyl ester, and sulfonate ester substituted coumarins 1-64 were screened for the inhibition of ROS, generated from zymosan activated whole blood phagocytes, using luminol-enhanced chemiluminescence technique. Among all tested compounds, 8 (IC50 = 65.0 ± 3.1 μM), 24 (IC50 = 41.8 ± 1.5 μM), 26 (IC50 = 10.6 ± 2.8 μM), 28 (IC50 = 20.9 ± 1.5 μM), and 41 (IC50 = 4.6 ± 0.3 μM) showed good anti- inflammatory potential as compared to standard antiinflammatory drug ibuprofen (IC50 = 54.3 ± 1.9 μM). Specifically, compounds 24, 26, 28, and 41 showed superior activity than standard antiinflammatory drug. Furthermore, compounds 12 (IC50 = 219.0 ± 1.4 μM), 14 (IC50 = 216.5 ± 6.2 μM), 16 (IC50 = 187.4 ± 2.2 μM), and 20 (IC50 = 196.2 ± 2.0 μM) showed moderate ROS inhibitory activity. Limited SAR study revealed that the hydroxy-substituted compound showed better ROS inhibition potential in case of 3-benzoyl and 3-ethylester coumarin derivatives. Whereas, chloro substitution was found to be important in case of 3-acetyl coumarin derivatives. Similarly, in case of sulfonate ester, chloro, and nitro groups especially at positions -4 and -3 of ring "R" played vital role in ROS inhibition. Furthermore, cytotoxicity of all active compounds was also checked on NIH-3T3 cell line. Compounds 12, 14, and 20 were found to be non-cytotoxic. Whereas, 8, 16, 24, 26, 28, and 41 were found to be very weak cytotoxic as compared to standard cycloheximide (IC50 = 0.13 ± 0.02 μM). Identified ROS inhibitors offer the possibility of additional modifications that could give rise to lead structures for further research in order to obtain more potent, and safer antiinflammatory agent.

Significance of the High Abundance of Pentacyclic Triterpenyl and Hopenyl Acetates in Sphagnum Peat Bogs from Northern Spain

Global warming is expected to increase the rate of CH4 emission from acidic peatlands leading to an increased interest on its mechanisms of formation. The main routes are through the reduction of CO2 by molecular hydrogen and through the cleavage of acetate. A predominance of the former, a reaction which also competes with homoacetogenesis to form acetate, may enrich the media in acetate, which could potentially be incorporated in the peat molecular markers. Acetates of triterpenoid biomarkers have been identified in peats and lake sediments and related to the input of higher plants. Nevertheless, the acetyl derivatives are found in very low amounts in fresh plants and in much lower amount than other derivatives with alcohol or ketone functional groups. The dichloromethane/methanol extracts of Asturian peat bog profiles (North Spain) were analyzed using gas chromatography/mass spectrometry (GC/MS) and compound-specific-isotope-analysis (CSIA). They show abundance of acetates of compounds with oleanane, ursane, and lupane skeletons derived from higher plants and with hopane skeleton, which can be considered a characteristic of these peats. Two families of 3-oxyhopenyl acetates with -17(21)- and -22(29)- configurations were detected in the upper part of the peat profiles, having a δ13C isotopic composition enriched by 4‰ compared with that of higher plant triterpenoids, and similar to that of microorganism-derived regular hopanoids. Both the acetate and ketone derivatives with the oxygenated functionality at C-3 were generally present in a given extract and tended to accumulate at certain depth in the profiles and in specific levels. The widespread occurrence of acetyl-derivatives, their higher concentration in the deeper layers of the peat, the fact that the acetates correspond to different compound families of diverse source and the very low amount of acetates identified in Ericaceae-contributing to the peat compared to the alcohols suggest that they were formed in the peat under particularly favorable environmental conditions. We postulate that these conditions could have been the existence of a medium enriched in acetic acid produced by the dominance of hydrogenotrophic methanogenesis and/or homoacetogenesis over acetoclastic methanogenesis. This phenomenon that has been preferentially described in Sphagnum bogs at high latitudes, and in the deeper layers of peat, appears to be also present in the temperate peats of the Asturian coast.