Search results for "Biomolecular"
showing 10 items of 507 documents
Flavouring Extra-Virgin Olive Oil with Aromatic and Medicinal Plants Essential Oils Stabilizes Oleic Acid Composition during Photo-Oxidative Stress
2021
Essential oils (EOs) from medicinal and aromatic plants (MAPs) are well-known as natural antioxidants. Their addition to extra-virgin olive oil (EVOO) can contribute to reducing fat oxidation. The main aim of this study was to improve both food shelf-life and aromatic flavour of EVOO, adding different EOs of Sicilian accessions of common sage, oregano, rosemary and thyme. The morphological and production characteristics of 40 accessions of MAPs were preliminarily assessed. EOs from the most promising accessions of MAPs were analysed by gas-chromatography and mass spectrometry. Photo-oxidative studies of the EOs were carried out and the determination of the EVOO fatty acids obtained from 4 I…
Interaction mechanism of endogenous PP2A inhibitor protein ENSA with PP2A
2022
The vast diversity of protein phosphatase 2A (PP2A) holoenzyme composition ensures its multifaceted role in the regulation of cellular growth and signal transduction. In several pathological conditions, such as cancer, PP2A is inhibited by endogenous inhibitor proteins. Several PP2A inhibitor proteins have been identified, one of which is α-endosulfine (ENSA). ENSA inhibits PP2A activity when it is phosphorylated at Ser67 by Greatwall (Gwl) kinase. The role of ENSA in PP2A inhibition is rather well characterized, but knowledge of the mechanism of inhibition is scarce. In this study, we have performed comprehensive structural characterization of ENSA, and its interaction with PP2A A- and var…
5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with effective carbonic anhydrase inhibitory activity: Solution and crystallographic investigat…
2017
Abstract A series of 5-substituted-benzylsulfanyl-thiophene-2-sulfonamides was prepared by reacting 5-bromo-thiophene-2-sulfonamide with 5-substituted-benzyl mercaptans. The new compounds were investigated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The cytosolic human (h) isoforms hCA I was poorly inhibited by the new sulfonamides (KIs in the range of 683–4250 nM), whereas hCA II, and the transmembrane, tumor associated isoforms hCA IX and XII were effectively inhibited in the subnanomolar–nanomolar range. A high resolution X-ray crystal structure of the adduct of hCA II with one of the new sulfonamides allowed us to rationalize the excellent inhibitory activity of these heterocycli…
Model of a six immunoglobulin-like domain fragment of filamin A (16-21) built using residual dipolar couplings.
2012
Filamins are actin-binding proteins that participate in a wide range of cell functions, including cell morphology, locomotion, membrane protein localization, and intracellular signaling. The three filamin isoforms found in humans, filamins A, B, and C, are highly homologous, and their roles are partly complementary. In addition to actin, filamins interact with dozens of other proteins that have roles as membrane receptors and channels, enzymes, signaling intermediates, and transcription factors. Filamins are composed of an N-terminal actin-binding domain and 24 filamin-type immunoglobulin-like domains (FLN) that form tail-to-tail dimers with their C-terminal FLN domain. Many of the filamin …
N-Substituted and ring opened saccharin derivatives selectively inhibit transmembrane, tumor-associated carbonic anhydrases IX and XII.
2017
A series of N-substituted saccharins incorporating aryl, alkyl and alkynyl moieties, as well as some ring opened derivatives were prepared and investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The widespread cytosolic isoforms CA I and II were not inhibited by these sulfonamides whereas transmembrane, tumor-associated ones were effectively inhibited, with KIs in the range of 22.1-481nM for CA IX and of 3.9-245nM for hCA XII. Although the inhibition mechanism of these tertiary/secondary sulfonamides is unknown for the moment, the good efficacy and especially selectivity for the inhibition of the tumor-associated over the cytosolic, widespread isoforms, make…
3H-1,2-benzoxathiepine 2,2-dioxides: a new class of isoform-selective carbonic anhydrase inhibitors
2017
Abstract A new chemotype with carbonic anhydrase (CA, EC 4.2.1.1) inhibitory action has been discovered, the homo-sulfocoumarins (3H-1,2-benzoxathiepine 2,2-dioxides) which have been designed considering the (sulfo)coumarins as lead molecules. An original synthetic strategy of a panel of such derivatives led to compounds with a unique inhibitory profile and very high selectivity for the inhibition of the tumour associated (CA IX/XII) over the cytosolic (CA I/II) isoforms. Although the CA inhibition mechanism with these new compounds is unknown for the moment, we hypothesize that it may be similar to that of the sulfocoumarins, i.e. hydrolysis to the corresponding sulfonic acids which therea…
Bomba rice conservation with a natural biofilm
2018
[EN] The chemical composition of commercial Syzygium aromaticum, Cinnamomum verum, and Laurus nobilis essential oils as well as their antifungal activity against four pathogenic fungi isolated from Mediterranean rice grains has been investigated. Eighty nine compounds accounting for between 98.5 and 99.4% of the total essential oil were identified. The phenylpropanoids eugenol (89.37 ± 0.29%) and eugenol (56.34 ± 0.41%), followed by eugenol acetate (19.48 ± 0.13%) were, respectively, the main compounds in clove and cinnamon essential oils, whereas large amounts of the oxygenated monoterpenes 1,8-cineole (58.07 ± 0.83%) and ¿-terpinyl acetate (13.05 ± 0.44%) were found in bay leaf essential …
GUI Implementation of VCDtools, A Program to Analyze Computed Vibrational Circular Dichroism Spectra
2020
As computing power increases, vibrational circular dichroism (VCD) calculations on molecules of larger sizes and complexities become possible. At the same time, the spectra resulting from these computations become increasingly more cumbersome to analyze. Here, we describe the GUI implementation into the Amsterdam Density Functional (ADF) software package of VCDtools, a toolbox that provides a user-friendly means to analyze VCD spectra. Key features are the use of the generalized coupled oscillator analysis methods, as well as an easy visualization of the atomic electric and magnetic transition dipole moments which together provide detailed insight in the origin of the VCD intensity. Using s…
Targeting the JAK/STAT Pathway: A Combined Ligand- and Target-Based Approach
2021
Janus kinases (JAKs) are a family of proinflammatory enzymes able to mediate the immune responses and the inflammatory cascade by modulating multiple cytokine expressions as well as various growth factors. In the present study, the inhibition of the JAK-signal transducer and activator of transcription (STAT) signaling pathway is explored as a potential strategy for treating autoimmune and inflammatory disorders. A computationally driven approach aimed at identifying novel JAK inhibitors based on molecular topology, docking, and molecular dynamics simulations was carried out. For the best candidates selected, the inhibitory activity against JAK2 was evaluated in vitro. Two hit compounds with…
Tanzawaic acid derivatives from freshwater sediment-derived fungus Penicillium sp.
2018
Abstract Chemical investigation of a freshwater sediment-derived fungus, Penicillium sp. (S1a1), led to the isolation of three new tanzawaic acid derivatives, including penitanzchroman (1), tanzawaic acids Y (2) and Z (3), along with six known tanzawaic acid analogues (4-9), three known isochromans (10-12) and two known benzoquinones (13 and 14). The structures of the new compounds were established based on high-resolution mass spectrometry, and detailed analysis of one- and two-dimensional NMR spectroscopy. The relative configuration of the new compounds was assigned on the basis of NMR spectroscopic data including ROESY spectra. The absolute configuration was determined based on the speci…