28,601 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
Plasma phospholipase, γ-CEHC and antioxidant capacity in fibromyalgia
No full textObjective: Recent studies have suggested a possible role of high levels of plasma lysophosphocholines (lysoPCs) in fibromyalgia syndrome (FMS). The aim of this study was to evaluate the content of plasma phospholipases (e.g., Platelet Activating Factor Acetyl Hydrolase [PAF-AH], secretory Phospholipase A2 [sPLA2], Total Antioxidant Capacity [TAOC] and 2,7,8-trimethyl-2-(2-carboxyethyl)-6-hydroxy chroman [c-CEHC]) in FMS patients and their association with clinical status and quality of life.
Methods: Thirty-six females meeting the 2011 American College of Rheumatology criteria for the classification of FMS and thirty-four healthy females were enrolled for the study. Plasma enzyme levels were quantified using commercial enzyme-linked-immunosorbent-assay (ELISA). In order to assess the disease severity and the functional status of patients, the Fibromyalgia Impact Questionnarie (FIQ) was used.
Results: Higher levels of sPLA2 and lower PAF-AH and c-CEHC were observed in the plasma of FMS patients compared to the controls. A decrease in PAF-AH and TAOC levels were found in severe FMS (S-FMS) compared to mild/slight (MS-FMS) forms.
Conclusion: The results of the study indicate a possible involvement of phospholipases and c-CEHC in fibromyalgia syndrome
Structural investigation of pig metmyoglobin by 129Xe NMR spectroscopy
No full textThe potentiality of xenon's sensitivity to its local magnetic environment is thoroughly investigated to probe internal structural differences between pig and horse metmyoglobin (MMb). These MMb's differ by 14 amino acids. One of these, Ile142 in horse MMb, is located in the proximal cavity, which is the xenon-binding site in horse MMb, and is replaced by Met142 in pig MMb. Specific and non-specific xenon-protein interactions are investigated here by Xe-129 NMR chemical shifts and relaxation rate in aqueous solutions of pig MMb as a function of the xenon and protein concentrations. The results are complemented with Xe-129 NMR data of the isostructural carbonmonoxy myoglobin (COMb), with computational calculations in order to highlight the structural differences between the cavities, and H-1 NMR spectra to test the dependence of the H-1 chemical shift on the addition of xenon. The Xe-129 chemical shift NMR parameters are analysed quantitatively in terms of a two-site model. Xenon forms a 1:1 complex with the protein, characterized by an equilibrium binding constant K=[Xe](in)/([Xe](out)[MMb]), and exchanges rapidly between a cavity within the protein (Xe-in) and all other environments (Xe-out). A comparison of equilibrium constant, K (74 M-1) in pig and K (146 M-1) in horse, reveals differences in affinity of xenon to the interior of pig MMb. Changes in xenon binding in both pig and horse MMb are also pointed out by other experimental results, e.g. the difference in the estimated delta(in), which is shifted downfield in pig MMb and upfield in horse MMb, with respect to Xe-129 in buffer solution; the xenon-iron distance, 7.4 Angstrom, which is longer in the pig than was found in the horse, 5.3 Angstrom
Identificazione e caratterizzazione di una doppia variante emoglobinica: Hb G-Philadelphia [68 (E17) Asn —› Lys] Hb Duarte [62 (E6) Ala —› Pro].
No full textSupercritical Extraction of Volatile and Fixed Oil from Petroselinum crispum L. Seeds. Chemical Composition and Biological Activity.
No full textSolution Structural Investigation of pig Metmyoglobin cavities and surface by 129Xe NMR Spectroscopy
No full text
<i>Euphorbia characias</i>: Phytochemistry and Biological Activities
No full textThe aim of this review is to summarize all the compounds identified and characterized from Euphorbia characias, along with the biological activities reported for this plant. Euphorbia is one of the greatest genera in the spurge family of Euphorbiaceae and includes different kinds of plants characterized by the presence of milky latex. Among them, the species Euphorbia characias L. is an evergreen perennial shrub widely distributed in Mediterranean countries. E. characias latex and extracts from different parts of the plant have been extensively studied, leading to the identification of several chemical components such as terpenoids, sterol hydrocarbons, saturated and unsaturated fatty acids, cerebrosides and phenolic and carboxylic acids. The biological properties range between antioxidant activities, antimicrobial, antiviral and pesticidal activities, wound-healing properties, anti-aging and hypoglycemic properties and inhibitory activities toward target enzymes related to different diseases, such as cholinesterases and xanthine oxidase. The information available in this review allows us to consider the plant E. characias as a potential source of compounds for biomedical research
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