Coumarin-type Compounds Research Articles

Effects of Coumarin-Type Compounds on Diabetes-Associated and Age-Related Sarcopenia

Effects of Coumarin-Type Compounds on Diabetes-Associated and Age-Related Sarcopenia

In silico evaluation for the design of coumarin-type compounds based on phenol and naphthol rings as a coating in carbon steel corrosion processes: DFT B3LYP calculations, synthesis and electrochemical characterization

Corrosion is a natural electrochemical process that converts metals into their most stable form, oxides. Coating metals with paints is done most effectively if oxide scales are removed, which is done by exposing the metals to corrosive media such as HCl, H2SO4, HNO3, and NaCl. However, corrosive solutions also attack the metal surface, and adding an inhibitor to the acid environment becomes necessary. Inhibitors can be inorganic or organic and are evaluated through techniques such as Potentiodynamic Polarization (PDP) and Impedance Spectroscopy (EIS). This work evaluated coumarin-type organic molecules compounds as potential corrosion inhibitors through the DFT B3LYP calculations of quantum descriptors. The results were analyzed using Principal Components Analysis (PCA), it is established that the values of inhibitory efficiency of 1, and 33, showed that the corrosion of the metallic surface which can be seen in the inhibitory efficiency values 1 (57,14 %) and 33 (82,86 %), it is evident that 33 has the highest effect respect other coumarins being identified as phenol and naphthol derivatives. These compounds were synthesized employing sequential reactions from the respective phenol: Pechmann cyclization, nitration, and reduction reactions. Then, the compounds were evaluated as anti-corrosive agents for carbon steel in the presence of 1.0 M HCl. The cathodic and anodic current densities in the HCl solution containing coumarin 1 exhibit lower values than the 33 and the Blank solutions. The obtained data reveals that as the amount of coumarins 1 (3.2 mg), and 33 (2.8 mg) increases, the corrosion current density (icorr) decreases to values of 3.08 and 4.90 mA.cm-2, respectively. These results were validated through the electrochemical evaluation of the molecules obtained by Potentiodynamic Polarization (PDP), Impedance Spectroscopy. (EIS) and Scanning Electron Microscopy (SEM).

A Widely Metabolomic Analysis Revealed Metabolic Alterations of Epimedium Pubescens Leaves at Different Growth Stages.

Epimedium folium is the major medicinally-used organ of Epimedium species and its metabolic changes during the leaf growth have not been studied at the metabolomic level. E. pubescens is one of five recorded species in the Pharmacopoeia of the People’s Republic of China and widely grows in China. A UPLC-ESI-MS/MS-based targeted metabolomic analysis was implemented to explore the metabolite composition in E. pubescens leaves under the cultivation condition and further to investigate their temporal variations among four representative growth stages. A total of 403 metabolites, including 32 hitherto known in Epimedium species, were identified in E. pubescens leaf, of which 302 metabolites showed the growth/development-dependent alterations. Flavonoid-type compounds were the major composition of the metabolites identified in this study. Most flavonoids, together with tannin-type and lignans and coumarin-type compounds, were up-regulated with E. pubescens leaf growth and maturation after the full flowering stage. Our results not only greatly enriched the existing Epimedium phytochemical composition database and also, for the first time, provided the metabolomics-wide information on metabolic changes during E. pubescens leaf growth and development, which would facilitate in the choice of an optimum harvest time to balance a higher biomass yield of Epimedium folium with its better medicinal quality.

Development of an in Silico Model of DPPH• Free Radical Scavenging Capacity: Prediction of Antioxidant Activity of Coumarin Type Compounds.

A quantitative structure-activity relationship (QSAR) study of the 2,2-diphenyl-l-picrylhydrazyl (DPPH•) radical scavenging ability of 1373 chemical compounds, using DRAGON molecular descriptors (MD) and the neural network technique, a technique based on the multilayer multilayer perceptron (MLP), was developed. The built model demonstrated a satisfactory performance for the training and test set , respectively. To gain greater insight on the relevance of the MD contained in the MLP model, sensitivity and principal component analyses were performed. Moreover, structural and mechanistic interpretation was carried out to comprehend the relationship of the variables in the model with the modeled property. The constructed MLP model was employed to predict the radical scavenging ability for a group of coumarin-type compounds. Finally, in order to validate the model’s predictions, an in vitro assay for one of the compounds (4-hydroxycoumarin) was performed, showing a satisfactory proximity between the experimental and predicted pIC50 values.

Secondary metabolites of Ferula foetida

The plant Ferula foetida Regel (Apiaceae) is broadly distributed in the flora of Central Asia [1]. It is well known in Eastern folk medicine and is still used as an anticonvulsant, expectorant, and antiflatulent for tuberculosis and syphilis and to improve digestion for gastrointestinal diseases in non-traditional medicine to treat various diseases [2–5]. Several S-containing aliphatic compounds, derivatives of thiophene, coumarins, and their derivatives in addition to several terpenes, were isolated from resin obtained from roots of this plant [6–9]. Several S-containing compounds, derivatives of thiophene and disulfides, were isolated earlier from the plant growing in Uzbekistan [8]. We studied the aerial part of F. foetida collected in Bukhar Oblast in the vicinity of Gazli during the generative phase (third year of growth) at the start of growth and during rapid development of leaf clusters, March through May, 2009. Air-dried samples were extracted with EtOH (85%, 6 ) to afford sample 1 (collected in March), yield of total extracted substances 18% of the plant weight; sample 2 (April), 17%; and sample 3 (May), 10%. Components of the dried EtOH extracts from the three samples in addition to juice from the aerial part of F. foetida were studied by GC-MS. According to TLC (hydrocarbons:EtOAc, 2:1), the second and third samples contained coumarin-type compounds whereas the first sample did not. Juice of F. foetida contained according to GC-MS data the principal components 2,3,4,5-tetramethylthiophene and 2-ethylthiopyridine. The extracts also contained 1,3-dimethyltrisulfane, 1,8-cineol (eucalyptol), S-methylmethanethiosulfonate, 2,3,4,5-tetramethylthiophene, (+)-trans-chrysanthenylacetate, (+)-calarene, bulnesol, etc. (Table 1).

APPLICATION OF HIGH-PERFORMANCE COUNTER CURRENT CHROMATOGRAPHY FOR SEPARATION OF COUMARINS FROM HERACLEUM MANTEGAZZIANUM

Coumarins are nowadays an important group of organic compounds from natural and synthetic sources that are useful in a number of fields. because they are known for different pharmacological properties, their separation and purification is a very important task. A high-performance counter-current chromatography (hPCCC) method is an efficient preparative technique offering a series of advantages over conventional chromatography like elimination of irreversible adsorption of sample or easy scaling-up. hPCCC method was applied for the preparative separation and purification of major coumarins from the fruits of Heracleum leskowii. A scale-up process from analytical to preparative in a very short time was developed. different experiments with mixtures of n-hexane, ethyl acetate, methanol and water in reverse phase system were performed. Coumarins such as angelicin, bergapten, imperatorin and some not unidentified coumarin-type compounds were obtained. The components purified and collected were analyzed by high-performance liquid chromatography with UV-dAd. Acknowledgments: This work was financially supported by Grant no N N405 617538 from the Polish Ministry of Science and Higher Education.

2-(Azidomethyl)arylboronic Acids in the Synthesis of Coumarin-Type Compounds

Several 2-(azidomethyl)arylboronic acids were synthesized. Their involvement into organolead-mediated Pinhey arylation reaction with 4-hydroxycoumarins afforded 3-[2-(azidomethyl)aryl]-4-hydroxycoumarins or [4,3-c]isoquinolino­coumarins in reasonable yields via two- or four-step one-pot reaction sequence. Palladium-catalyzed cross-coupling of organoboron reagents with 4-trifluoromethylsulfonyloxycoumarins under Suzuki reaction conditions gave 4-[2-(azidomethyl)aryl]coumarins in good yields. 2-(Azidomethyl)arylboronic acid, as well as azide-containing iso- and neoflavonoid compounds underwent catalytic alkyne-azide cycloaddition in THF-water, providing 1,4-triazole compounds regioselectively in good to excellent yields.

Computer-assisted, high-performance liquid chromatography with mass spectrometric detection for the analysis of coumarins in Peucedanum palustre and Angelica archangelica.

A reversed-phase HPLC method with atmospheric pressure chemical ionisation MS detection has been developed for the separation and identification of coumarins in plants of Peucedanum palustre L. (Moench) and Angelica archangelica (L.) var. archangelica. The Turbo Method Development program was utilised to optimise the mobile phase with two organic solvents (acetonitrile and methanol) and two aqueous solutions (1.0% formic acid and 10 mM ammonium acetate). Optimisation of the solvent gradients for the method was performed with the aid of the DryLab program. Analyses were carried out using a Phenomenex Prodigy RP C18 column. Fifty-two peaks (14 of which were associated with coumarins) were separated in 30 min from extracts of P. palustre, and 48 peaks (15 associated with coumarins) from extracts of A. archangelica. A total of 21 different coumarin-type compounds were identified in the aerial and the underground parts of the title plants. Isopimpinellin and pimpinellin were found for the first time in P. palustre and were identified by comparison of retention times and MS data obtained following the analysis of pure standards. This is the first report of the coumarin composition of the umbels of P. palustre.

New fluorogenic substrate for the first continuous steroid sulfatase assay

The screening for new inhibitors of steroid sulfatase requires an efficient test system. To overcome the shortcomings of the available discontinuous fluorimetric assay, several coumarin-type compounds were investigated as potential new substrates. 3,4-Benzocoumarin 7-O-sulfate was found to have appropriate substrate properties for the establishment of the first direct continuous assay of steroid sulfatase.

Insecticidal effectiveness ofMammea Americana (Guttiferae) extracts on larvae ofDlabrotica Virgifera Virgifera (Coleoptera:Chrysomelidae) andTrichoplusia Ni (Lepidoptera:Noctuidae)

Seed and leaf extracts ofMammea americana (mamey apple) have a historical use as a biopesticide with the active components previously characterized. We reexamined the utility of this natural bioinsecticide in light of existing sources of material as a by-product of the fruit processing industry. Our results addDiabrotica virgifera virgifera andTrichoplusia ni to the list of insects which are susceptible to the insecticidal ingredients ofM. americana and confirms earlier reports of activity againstBlatella germanica, Periplaneta americana, andPlutella xylostella. We report LD5Os for crude hexane extracts ofM. americana leaves and seeds againstT. ni. These materials represent renewable sources of bioinsecticides for agriculture, and should regenerate interest in coumarin-type compounds for novel pesticidal action.

Differential inhibition of coumarin 7-hydroxylase activity in mouse and human liver microsomes

Coumarin is 7-hydroxylated by the P450 isoform Cyp2a-5 in mice and CYP2A6 in humans. Various drugs, endogenous substances, plant substances and carcinogens, altogether about 90 chemicals. were evaluated as possible inhibitors of coumarin 7-hydroxylase (COH) activity in mouse microsomes. The effects of selected compounds on COH activity in human liver microsomes were also tested. The furanocoumarin derivatives methoxsalen (8-methoxypsoralen) and psoralen proved to be the most potent inhibitors of mouse COH activity (IC 50 values 1.0 and 3.1 μM, respectively). The furanocoumarins bergapten (5-methoxypsoralen), isopimpinellin (5,8-dimethoxypsoralen), imperatorin and sphondin also effectively inhibited mouse COH activity ( ic 50 values 19–40 μM). Methoxsalen, isopimpinellin and metyrapone were also inhibitors in mice in vivo. Methoxsalen was a potent inhibitor of COH activity also in human liver microsomes ( ic 50 value 5.4 μM), whereas bergapten, isopimpinellin and imperatorin had no effect. The imidazole antimycotic miconazole was a potent but non-specific inhibitor of COH activity. Several known substrates and inhibitors of members in the CYP1A, CYP2B, CYP2C, CYP2D and CYP3A subfamilies were poor inhibitors of COH activity. These results suggest that (i) the coumarin-type compounds in particular interact with the active sites of Cyp2a-5 and CYP2A6, and (ii) the active sites of Cyp2a-5 and CYP2A6 are structurally different, since a number of compounds inhibited mouse, but not human COH activity.

A guide to anticoagulant therapy.

The physician who undertakes anticoagulant therapy tampers with one of the most important homeostatic functions of the body. In so doing, he subjects the patient to the calculated hazard of possible hemorrhage balanced against the risks of the thrombosis or embolism that he seeks to prevent or treat. Agents currently employed are heparin and coumarin-type compounds. These two categories of anticoagulants act at different sites of the coagulation mechanism, are administered differently, are metabolized differently, are reversed by different antidotes, and their effects are measured by different tests. Certain facts about which the physician should be adequately informed have been presented regarding the hemostatic mechanism; the physiology and pharmacology of the anticoagulants, especially as they may explain the wide variation in individual response; certain aspects of methodology; and the various practical problems involved in therapeutic management. Emphasis has been placed on the importance of individualization of treatment, careful clinical observation, and frequent reliable laboratory tests as guides to proper therapy.