1,720,965 research outputs found
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
The synthesis of procyanidin B3 and heterocycle-linked oligonucleotides
No full textThe first section of this thesis describes the synthesis of procyanidin B3, a dimeric flavanoid consists of monomeric (+}-catechin and a member of the polyphenol family. A study of the leaving groups at C4 catechin together with Lewis acid activator effects on the formation of the interflavan hond formation was conducted. A range of electrophilic ethers was prepared via DDQ oxidation and a1coholic trapping (propanol, crotyl a1rohol and propargyl alcohol) at the C4 position of (+}-catechin. The Lewis acid-mediated nucleophilic C4 substitution of each of these ethers was examined and it was found that the propargyl ether was the best overall e1ectrophile. A range of Lewis acids were then examined as activators and it was found that BF3oOEt2 was the best in terms of both yield and stereochemical control at the C4 position. In our view, the strength of the nucleophiles used contributed mainly to the diastereoselectivity preference for the substitution reactions. This newly developed set of conditions was then used to prepare the natural product nutraceutical procyanidin B3 with high control of diastereoselectivity. To extend the versatility of this synthesis, a novel dimeric polyphenol analogue was synthesised utilising the optimum conditions used for the synthesis of pro cyanidin B3. The second section of this thesis is devoted to the synthesis of novel morpholino antisense oligonucleotides. Herein, the synthesis of amine and amide triazolelinked Morpholinos (TI.Morpholinos) using click copper-catalysed Huisgen [3 + 2] cycloaddition is illustrated. Replacing the charged phosphodiester backbone with a neutral, achiral 1.2.3-triazole linkage was chosen to improve the biostability in antisense applications. The synthesis of terminal alkyne morpholinos and examples of azide monomers required for the click chemistry was successfully achieved. The synthesis presented in this work tolerated a range of functionalities and was amenable to all nucleosides. The amine and amide TI.Morpholino oligonucleotides were constructed using the standard solid-phase DNA synthesis. Both the amine and amide TLMorpholinos formed were characterised by MALDITOF and HPLC experiments. The thermal stability of the amine and amide TI.Morpholinos relative to a standard DNA was assessed and it was found that the amine and amide triazole linkages stabilised the DNA duplex. It was concluded that these modifications enhanced the stability of the DNA duplex and consequently might contribute to the development of new candidates for the antisense applicationsEThOS - Electronic Theses Online ServiceGBUnited Kingdo
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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