Search results for "010404 medicinal & biomolecular chemistry"
showing 10 items of 373 documents
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…
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…
Aging Successfully: The Role of Genetics and Environment in the Era of the Aging-Boom. Potential Therapeutic Implications
2019
Aging is one of the main health-related challenges in the world. The average life expectancy of the global population at birth is increasing up to 72 years, in 2016 and it increases about two years every decade. The healthcare costs in many countries are very high because of the increased number of unhealthy populations, and the consequent increase of severe age-related disabilities [1]. Therefore, the goal of the future should be the achievement of the so-called “health-span” (healthy-life-span), more than the treatment of age-related disease to prevent the collapse of the health system. In order to achieve this objective, it is necessary to identify new targets and biomarkers and to addre…
Genotypic and phenotypic aspects of longevity: results from a Sicilian survey and implication for the prevention and the treatment of age-related dis…
2019
Background:It is well known that long living individuals are a model of successful ageing and that the identification of both genetic variants and environmental factors that predispose to a long and healthy life is of tremendous interest for translational medicine.Methods:We present the preliminary findings obtained from an ongoing study on longevity conducted on a sample of Sicilian long-lived individuals.Results:We review the characteristics of longevity in Sicily, taking into account lifestyle, environment, genetics, hematochemical values, body composition and immunophenotype. In addition, we discuss the possible implications of our data for the prevention and/or treatment of age-related…
Neuroprotective potential of Ginkgo biloba in retinal diseases
2019
AbstractLike other tissues of the central nervous system, the retina is susceptible to damage by oxidative processes that result in several neurodegenerative disease such as age-related macular degeneration, diabetic retinopathy, glaucoma, ischaemic retinal disease, retinal disease produced by light oxidation, and detached retina, among other diseases. The use of antioxidant substances is a solution to some health problems caused by oxidative stress, because they regulate redox homeostasis and reduce oxidative stress. This is important for neurodegeneration linked to oxidation processes. In line with this, Ginkgo biloba is a medicinal plant with excellent antioxidant properties whose effect…