2,351 research outputs found
Butyrylcholinesterase Inhibitors: Structure-Activity Relationships of 2-Phenylbenzofuran derivatives.
No full textButyrylcholinesterase Inhibitors: Structure-Activity
Relationships of 2-Phenylbenzofuran derivatives
Antonella Fais1*, Giovanna L. Delogu 1, Benedetta Era 1, Amalia Di Petrillo1,
Amit Kumar2,3, Paola Caria4, Sonia Floris1, Francesca Pintus1
1Department of Life and Environmental Sciences, University of Cagliari , Cagliari , Italy;
2Department of Mech., Chem. and Material Engineering , University of Cagliari , Cagliari , Italy;
3Biosciences Sector, CRS4 ,Pula , Italy
4Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
*Corresponding author: [email protected]
Alzheimer’s disease (AD) is an irreversible and progressive brain disorder which is characterized by
progressive memory loss and a wide range of cognitive impairments.1 Although the precise cause of AD is
not completely known, there are some factors that seem to play a significant role in the pathogenesis of AD.
Since AD is characterized by a forebrain cholinergic neuron loss and a progressive decline in acetylcholine, a
possible therapeutic strategy involves the use of cholinesterase (ChE) inhibitors to restore the
neurotransmitter level and thus alleviate AD symptoms.2
Benzofuran scaffold has drawn considerable attention over the last few years due to its profound
physiological and chemotherapeutic properties. Recent studies have also investigated their inhibitory activity
towards ChEs.3,4
In this study, a series of 2-phenylbezonfurans compounds were synthesized and their inhibition
activity towards the ChE enzymes were investigated. We further combined biochemical analysis and
molecular modelling studies to identify selective butyrylcholinesterase (BChE) inhibition by benzofuran
scaffold. In particular, two compounds exhibited the highest BChE inhibition with IC50 values better than the
standard cholinesterase inhibitor compound. Molecular modelling studies highlighted the importance of
catalytic and peripheral site residues in BChE inhibition. Subsequently, the biosafety of the two promising
compounds was evaluated, in NSC-34 cells at the concentration in which BChE activity is inhibited, and no
considerable cytotoxic effect was found.
References
1. Schuster et al. Bioorg. Med. Chem. (2010) 18, 5071.
2. Zemek et al. Expert Opin Drug Saf (2014) 13, 759.
3. Mostofi et al. Eur. J. Med. Chem. (2015) 103, 361.
4. Delogu et al. Bioorg. Med. Chem. (2016) 26, 2308
On the biphasic nature of the N400-P600 complex underlying language comprehension
No full textThis repository contains data and code from Delogu, Aurnhammer, Brouwer & Crocker, 2025, Brain & Cognitio
Evaluation of Adults With Congenital Heart Disease
No full textThe clinical approach to adults with congenital heart diseases (ACHDs) is unique
in cardiovascular medicine because these patients encompass a broad range of
presentations. Each patient, despite having similar diagnosis, will be
anatomically and physiologically unlike others within ACHD population, in
relation to the type of repair, age at repair, associated defects, with specific
long-term risk factors and complications. Furthermore, as many patients will not
complain of symptoms, clinical evaluation and diagnostic testing must also be
based on the underlying main diagnostic category, with complete standardized
lesion-specific clinical protocols, investigating all known risk factors specific
for each congenital heart disease and performed as part of screening for
significant long-term complications. The first part of this review will focus on
clinical history, physical examination, and the most important diagnostic testing
in ACHD population. The second part of the article will focus on some clinical
issues we have to face in our daily practice, such as heart failure, cyanosis,
and pulmonary hypertension. Furthermore, as survival rates of ACHD population
continue to improve and patients with this condition live longer, we will briefly
report on a new clinical concern regarding the impact of acquired morbidities
like coronary artery disease that appear to be of greater importance in defining
outcome in older patients with ACHD
Synthesis and biological activity of 2-phenylbenzofuran derivatives as butyrylcholinerase inhibitors
No full textAlzheimer disease (AD) is an irreversible and progressive brain disorder characterized by progressive memory loss and a wide range of cognitive impairments. An accepted strategy towards its treatment is to restore the levels of acetylcholine by inhibiting cholinesterase enzymes, such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). BChE activity progressively increases in patients with AD, while AChE activity remains unchanged or declines, with changes that become more and more pronounced during the disease course. Therefore, compounds that selectively interact with BChE might have a relevant role in treatment of patients with advanced AD.
Benzofuran scaffold has drawn considerable attention over the last few years due to its profound physiological and chemotherapeutic properties. In our recent study, a series of 2-phenylbezonfurans compounds were synthesized and their inhibition activity towards both the enzymes were investigated. These compounds showed no inhibition toward AChE while inhibited BChE with different efficiencies. In addition to biological assays, molecular dynamics simulations allowed highlighting the molecular basis of the selective BChE inhibition by the benzofuran scaffold.
Based on these previous results, in the current work we have designed new 2-benzofurans derivatives in order to increase the strength of enzyme inhibition. We have used the Wittig reaction as a key step of a good methodology for the efficient and general synthesis of a selected series of 2-phenylbenzofurans. For all the compounds of the series, the IC50 values were determined.
In this scenario, our findings could be extended to design and develop new potentially therapeutic molecules, especially useful in neurodegenerative diseases
Maintenance and manipulation of object sequences in working memory: a lifespan study
No full textMany studied reported that working memory components receive remarkable changes during lifespan. In order to better investigate this, we evaluated working memory components on human subjects belonging to five groups (10 subjects each) at different ages 6, 8 and 10 years old, young adult (age) and old adult (age). Our pattern of results shows a major transition in object sequence manipulation performance between ages 8 and 10 years. If related to young adults results, both 10-year-old children and old adults differed in accuracy and RT in both maintenance and manipulation conditions. In particular, young adults and old adults differ in RTs in the manipulation condition. Our results also suggest that a change in response strategy from 6 to 8 years of age, to prioritize accuracy may be present. Our findings appear consistent with recent neuroscientific findings, and lead to novel predictions
Effects of intensionality on sentence and discourse processing: evidence from eye-movements
No full textIntensional verbs like want select for clausal complements expressing propositions, though they can be perfectly natural when combined with a direct object. There are two interesting phenomena associated with intensional transitive expressions. First, it has been suggested that their interpretation requires enriched compositional operations, similarly to expressions like began the book (e.g., Pustejovsky, 1995). Secondly, when the object position is filled by an indefinite NP, it preferentially receives an unspecific reading, under which definite anaphora is not supported (e.g., Moltmann, 1997). We report three eye-tracking experiments investigating the time-course of processing of sentence pairs like John wanted a beer. The beer was warm. Consistent with the enriched composition hypothesis, results showed that intensional transitive constructions (e.g., wanted a beer) take longer to process than control expressions (e.g., drank/wanted to drink a beer). However, contrary to previous findings, the processing of the continuation sentence appears to be not affected by whether the definite NP (the beer) can be interpreted as coreferential with the indefinite or not. We interpret the results with respect to accounts of semantic processing relying on the notions of enriched composition and non-actuality implicatur
"The love that made hell, paradise." Ouida re-writing the Paolo and Francesca theme in Held in Bondage
No full textThe bestselling Victorian author Ouida reveals in her novels, and, in particular, Held in Bondage, an extraordinary knowledge od Dante, by using characters and themes from the Commedia. The Paolo and Francesca theme actually constitutes part of the plot of the novel and is to be found in many of her other works, short stories and non-fiction writing
Pistacia lentiscus: phytochemistry and anti-diabetic properties
No full textPistacia lentiscus L. (P. lentiscus) is an evergreen shrub (Anacardiaceae family) primarily found in the Mediterranean region. The plant has been thoroughly characterized, resulting in a high concentration of bioactive compounds as flavonoids and phenolics. Moreover, P. lentiscus was revealed to possess a great nutritional and industrial importance because of its variety of biological activities, including antibacterial, anti-inflammatory, anti-atherogenic and antioxidant properties. Many of its beneficial health properties and applications date back to antiquity, and the European Medicines Agency officially acknowledged it as an herbal medicinal product. Indeed, it is widely employed in conventional medicine to treat several diseases, including type 2 diabetes (T2D). On this basis, this review aims to summarize and describe the chemical composition of different parts of the plant and highlight the potential of P. lentiscus, focusing on its antidiabetic activities. The plant kingdom is drawing increasing attention because of its complexity of natural molecules in the research of novel bioactive compounds for drug development. In this context, P. lentiscus demonstrated several in vitro and in vivo antidiabetic effects, acting upon many therapeutic T2D targets. Therefore, the information available in this review highlighted the multitarget effects of P. lentiscus and its great potential in T2D treatment
HERStory Makers 2023: Francesca Fotheringham
No full textFrancesca Fotheringham is a postdoctoral research associate at the University of Edinburgh studying educational psychology with a focus on neurodiversity. She took part in HERStory Makers 2023.What is HERStory Makers?HERStory Makers is a social media competition for female-identifying early career researchers to share their research, their career journeys, and to inspire the next generation. Winners are selected by public vote. HERStory Makers is also part of EXPLORATHON, Scotland's contribution to European Researchers' Night.In 2022-23, EXPLORATHON Francescasupported by the Engineering & Physical Sciences Research Council [grant number EP/X020762/1].Author contributions to contentFrancesca conceived, planned, and recorded the video content. Kirsty Ross edited the video content to insert HERStory Maker credits, added subtitles, and reduce video length to below Twitter/X limit of 2 mins and 20 secs.</p
Discourse Expectations Are Sensitive to the Question Under Discussion: Evidence From ERPs
No full textQuestions under Discussion (QUDs) have been suggested to influence the integration of individual utterances into a discourse-level representation. Previous work has shown that processing ungrammatical ellipses is facilitated when the elided material addresses an implicit QUD raised through a nonactuality implicature (NAIs). It is not clear, however, if QUDs influence discourse coherence during comprehension of fully acceptable discourse. We present two ERP studies examining the effects of QUDs introduced by NAIs using two-sentence discourses. Experiment 1 showed that processing definite NPs with inaccessible antecedents is facilitated when their content is relevant to the QUD. Using acceptable discourses, Experiment 2 showed that definite NPs failing to address a QUD elicit increased processing cost. Overall, our results indicate that QUDs raise the expectation that the following discourse will address them, providing unambiguous evidence that their influence is not limited to the processing of ungrammatical input
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