1,721,361 research outputs found
Novel piperazine and morpholine substituted quinolines: Selective synthesis through activation of 3,6,8-tribromoquinoline, characterization and their some metabolic enzymes inhibition potentials
No full textTaslimi, Parham/0000-0002-3171-0633; Okten, Salih/0000-0001-9656-1803Regioselective routes are described for convenient preparation of novel piperazine/morpholine substituted quinoline derivatives at C-3, C-6 and C-8 starting with 3,6,8-tribromoquinoline (6) by nucleophilic substitution via conventional heating or microwave assisted reaction conditions. 3,6,8-Tribromoquinoline (6) was treated with piperazine and morpholine under microvawe irradiation, which selectively furnished 3-mopholinyl and 3-piperazinyl quinoline derivatives 7 and 8 in yields of 58% and 60%, respectively. On the other hand, the activation of benzene cycle of quinoline by nitration of 3,6,8-tribromoquinoline, giving 5-nitro-3,6,8-tribromoquinoline (18) in quantitative yield, was enabled. Then, the bromines at C-6 and C-8 were selectively exchanged by morpholine and piperazine via SNAr reactions. Thus, 6,8-dimopholinylquinoline (22) and 5-nitro-6,8-dipiperazinylquinoline (24), biologically valuable derivatives, were prepared in high yields (82% and 72%, respectively). The synthesized compounds were fully characterizated by H-1 NMR, C-13 NMR, 2D NMR, XRD, HRMS and IR spectra. The novel molecules had effective inhibition profiles against some metabolic enzymes. Also, they have the potential of drug candidates to treat of some diseases including glaucoma, epilepsy, Alzheimer's disease (AD), leukemia, and type-2 diabetes mellitus (T2DM). (C) 2020 Elsevier B.V. All rights reserved.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [112T394]This study was financially supported by grants from the Scientific and Technological Research Council of Turkey (TUBITAK, Project number: 112T394). The authors thank to Scientific and Technological Research Application and Research Center, Sinop University, Turkey, for the use of the Bruker D8-QUEST diffractometer
Assessments of anticholinergic, antidiabetic, antioxidant activities and phenolic content of Stachys annua
No full textGoren, Ahmet C/0000-0002-5470-130X; Taslimi, Parham/0000-0002-3171-0633Some biochemical properties including phenolic content, anticholinergic, antidiabetic, and antioxidant activities of Stachys annua were determined in this study. The methanol extract of Stachys annua (MESA) and the water extract of Stachys annua (WESA) were prepared and used for all biochemical analyses. Antioxidant capacities of MESA and WESA were evaluated by six different in vitro bioanalytical methods including three reducing antioxidant methods and three radical scavenging antioxidant methods. Also, enzyme inhibition effect of Stachys annua against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), alpha-amylase, and alpha-glycosidase enzymes were determined separately. According to the results, both extracts showed high inhibition effects against alpha-amylase and alpha-glycosidase enzymes, whereas they showed low inhibition effects against AChE and BChE enzymes. The IC50 values of MESA and WESA against AChE (119.8 +/- 2.4 mu g/mL and 150.1 +/- 3.0 mu g/mL), BChE (192.1 +/- 3.8 mu g/mL and 186.7 +/- 3.7 mu g/mL), alpha-glycosidase (25.7 +/- 0.5 mu g/mL and 18.7 +/- 0.4 mu g/mL), and alpha-amylase (43.3 +/- 0.9 mu g/mL and 11.4 +/- 0.2 mu g/mL) were determined, respectively. Another goal of the study was to evaluate the phenolic compositions of Stachys annua by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Quercetagetin-3,6-dimethylether (178.6 +/- 33.5 mu g/g), chlorogenic acid (118.2 +/- 16.4 mu g/g), and fumaric acid (102.5 +/- 7.1 mu g/g) were identified as major compounds in MESA. On the other hand, fumaric acid (309.5 +/- 21.5 mu g/g), apigenin (144.6 +/- 11.7 mu g/g), and chlorogenic acid (78.1 +/- 10.8 mu g/g) were identified as major compounds in WESA. This study will be a scientific base for further studies about Stachys annua for food or medicinal utilization
Synthesis of 6-ethoxyphenyl 4-fluorobenzenesulfonate-tagged thiosemicarbazones as carbonic anhydrase inhibitors: In-vitro and in silico approach
No full textIn this study, a series of 6-ethoxyphenyl-4-fluorobenzenesulphonate-based thiosemicarbazones (5a–w) were synthesized via a two-step process and structurally characterized by 1H NMR and 13C NMR spectroscopy. Their inhibitory activities against human carbonic anhydrase isoforms I and II (hCA I and hCA II) were evaluated, revealing potent inhibition at low nanomolar concentrations with IC50 values ranging from 56.36 to 230.17 nM for hCA I and 30.66 to 175.45 nM for hCA II. Compounds 5a, 5g, and 5n exhibited the highest enzyme inhibition, with 5a identified as the most potent in vitro inhibitor for both isoforms. Molecular docking studies and MM-GBSA binding free energy calculations demonstrated that compound 5n displayed the strongest binding affinity toward hCA I, stabilized by key interactions including π-π stacking, hydrogen bonds, and coordination to the catalytic zinc ion. Molecular dynamics simulations over 100 ns confirmed the stability and dynamic adaptability of the 5n–hCA I and 5g–hCA II complexes, preserving critical interactions essential for binding. Validation of the docking protocol yielded RMSD values below 2.0 Å, supporting the reliability of the computational approach. Overall, these findings highlight compounds 5n and 5g as promising lead molecules for selective inhibition of hCA I and hCA II, with potential applications in the treatment of carbonic anhydrase-related disorders
Design, Synthesis, In Vitro, and In Silico Studies of 5‐(Diethylamino)‐2‐Formylphenyl Naphthalene‐2‐Sulfonate Based Thiosemicarbazones as Potent Anti‐Alzheimer Agents
No full textAlzheimer's disease (AD) is known as one of the more devastating neurodegenerative diseases diagnosed in older people. Cholinesterase inhibitors (ChEI) can be used as an effective palliative treatment for AD. An extensive range of new biologically active 4-(diethylamino) salicylaldehyde-based thiosemicarbazone derivatives 5(a–u) was synthesized and evaluated as inhibitors of cholinesterase (ChE) and monoamine oxidase (MAO) enzymes. 2,3-Dichloro-substituted compound 5u was the most potent inhibitor of AChE and MAO-A with IC50 values of 12.89 and 96.25 nM, respectively. In contrast, the 2,3-dichlorophenyl-substituted compound 5a was the most powerful inhibitor of BChE, with an IC50 value of 124.72 nM. Structure–activity analysis revealed that the electron-withdrawing substituents on the phenyl ring play a crucial role in the inhibition potential of synthesized compounds. Compound 5a showed the strongest binding with 4BDS (−11.3 kcal/mol) via hydrogen bonds and π-interactions. Compound 5u exhibited high affinity with 1B41 (−8.2 kcal/mol), 2Z5X (−8.6 kcal/mol), and 2V5Z (−7.8 kcal/mol), forming key hydrogen bonds, salt bridges, and π-interactions, highlighting its multi-target potential. In silico ADME, pharmacokinetics, and drug-likeness studies were conducted and compared with the standard drugs galantamine and clorgyline
Anticholinergic, antidiabetic and antioxidant activities of Anatolian pennyroyal (Mentha pulegium)-analysis of its polyphenol contents by LC-MS/MS
No full textGoren, Ahmet C/0000-0002-5470-130X; Taslimi, Parham/0000-0002-3171-0633Methanol and water extracts of pennyroyal (Mentha pulegium) were evaluated for their antioxidant profiles by eight distinguished bioanalytical methods and for their inhibitory effects against enzymes linked to different diseases, namely acetylcholinesterase, butyrylcholinesterase, alpha-glycosidase and alpha-amylase. Additionally, the antioxidant properties of both extracts were determined and their polyphenolic compositions were evaluated by LC-MS/MS. For estimation of the antioxidant capacities of methanolic extract of pennyroyal (MEP) and water extract of pennyroyal (WEP); 2,2' -azino-bis-3-ethylbenzthiazoline-6-sulphonic acid radical (ABTS(center dot+)), 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH.), and N,N-dimethyl-p-phenylenediamine (DMPD center dot+) scavenging activities, Fe3+-2,4,6-tris(2-pyridyl)-s-triazine (TPTZ), Fe3+, and Cu2+ reducing assays were studied. The IC50 values of the MEP and WEP indicated that they were potent effective DPPH center dot (16.92 and 18.52 mu g/mL), ABTS(center dot+) (7.92 and 9.37 mu g/mL) and DMPD center dot+ (36.02 and 38.94 mu g/mL) scavengers, as well as acetylcholinesterase (AChE) (40.76 and 60 mu g/mL), butyrylcholinesterase (BChE) (49.51 and 63.03 mu g/mL), alpha-glycosidase (20.38 and 21.65 mu g/mL) and alpha-amylase (23.11 and 36.47 mu g/mL) inhibitors. Plant materials are potential sources for novel products in food and pharmaceutical applications. Also, biologically active compounds from plants have proven to be desirable in cosmetics, foods, and pharmaceuticals. This study clearly showed that both MEP and WEP had a broad screening of active compounds and phytochemicals. As a result of this abundant active ingredient, both extracts possessed antioxidant, anticholinergic and anti-diabetes properties.King Saud University, Saudi ArabiaKing Saud University [RSP-2019/59]S.H.A would like to extend his sincere appreciation to the Researchers Supporting Project (RSP-2019/59), King Saud University, Saudi Arabia
Evaluation of in vitro inhibitory effects of some natural compounds on tyrosinase activity and molecular docking study: Antimelanogenesis potential
No full textTyrosinase enzyme is a functional oxidase that is extensively divided in nature. It is the main enzyme in melanin synthesis and is also involved in designating the color of mammalian hair and skin. Additionally, it is accountable for the unfavorable enzymatic browning that happens in plant-derived foods, limiting the shelf-life of new-cut crops with the resultant economic harm. Recently, there has been a remarkable concern to study the inhibitory activity of the tyrosinase enzyme and some inhibitory molecules isolated from natural sources. For tyrosinase enzyme, afzelin, narcissoside, justiciresinol, thalassiolin B, carpachromene, neobavaisoflavone, and kojic acid (as standard) as natural phenols have IC(50)values in the range of 2.37-7.90 mu M. Theoretical methods, such as gaussian software program and molecular modeling, were used to compare the biological and chemical activity values of molecules. To compare the biochemical and chemical activity values of molecules, chemical activities with quantum chemical parameters, and biological activities against tyrosinase with the ID of 5M8L molecules were investigated
In vitro inhibitory effects of some acetophenone derivatives on some metabolic enzymes and molecular docking
No full textIn this study, the acetophenone derivatives1-6were found to be effective inhibitor molecules for alpha-glycosidase, human carbonic anhydrases I and II (hCA I/II), and acetylcholinesterase (AChE), withK(i)values in the range of 167.98 +/- 25.06 to 304.36 +/- 65.45 mu M for alpha-glycosidase, 555.76 +/- 56.07 to 1,043.66 +/- 98.78 mu M for hCA I, 598.63 +/- 90.04 to 945.76 +/- 74.50 mu M for hCA II, and 71.34 +/- 11.25 to 143.75 +/- 31.27 mu M for AChE, and IC(50)values of 73.65-101.13 mu M for tyrosinase. In the last step, molecular docking calculations were performed to compare the biological activities of molecules with their docking scores in these enzymes. The interactions of the studied molecules against human alpha-galactosidase (PDB ID: 1R47), hCA I (PDB ID: 3LXE), human AChE (PDB ID: 4M0E), hCA II (PDB ID: 5AML), and human tyrosinase (PDB ID: 5M8Q) were examined to compare the biological activity values. The ADME/T analysis (adsorption, distribution, metabolism, and discharge) was then performed for the future use of these molecules as drugs
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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