Synthesis of some westphalen-type cardenolide analogs

1982 ◽  
Vol 47 (1) ◽  
pp. 108-116 ◽  
Author(s):  
Pavel Kočovský ◽  
Pavel Drašar ◽  
Vladimír Pouzar ◽  
Miroslav Havel
Keyword(s):  
Lactone Ring ◽  
Cardiotonic Activity ◽  
Unsaturated Lactone ◽  
Tributyltin Hydride ◽  
Key Steps

Synthesis of the lactone II and thiazole XXIII as models of compounds with cardiotonic activity is described. The key steps in the synthesis of the lactone II are Westphalen rearrangement (XII - XIII), construction of unsaturated lactone ring by intramolecular Witting reaction (XV XIX) and removal of the halogen from 6β-position by reduction with tributyltin hydride. XXIII was obtained from the bromo ketone XXII by treatment with ethyl thioxamate.

Abstract 90: Inimitable Ouabain: The Endogenous Circulating Cardiotonic Steroid that Singularly Stimulates Sodium Potassium Pump Activity at Low Doses

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Yeon Jae Kim ◽  
Elisha Hamilton ◽  
William Hannam ◽  
Chia-Chi Liu ◽  
Rachel Teh ◽  
...  
Keyword(s):  
Low Dose ◽  
Lactone Ring ◽  
Cardiac Contractility ◽  
Cancer Cell Line ◽  
Structural Components ◽  
Sodium Potassium ◽  
Sugar Moiety ◽  
Unsaturated Lactone ◽  
Sodium Potassium Pump ◽  
The Difference

Rationale: Cardiotonic steroids (CTS), such as digoxin, have been used to treat heart failure (HF) for over 200 years. They inhibit the sodium-potassium pump (NKP), and increase cardiac contractility by inhibiting efflux of sodium through the pump (“digitalis hypothesis”). CTS possess three structural components: a saturated/unsaturated lactone ring, steroid core, and sugar moiety, each of which may be involved in NKP inhibition/stimulation. It is now known that inhibition of the NKP in patients with HF increases mortality, and all major beneficial treatments increase its activity. Endogenous circulating CTS such as ouabain are generally thought to inhibit the NKP, despite studies sporadically reporting ouabain-induced pump stimulation. This study aims to identify whether ouabain-induced pump stimulation occurs, and if so, which structural components are involved in causing pump stimulation. Methods & Results: Cardiac myocytes were isolated from male New Zealand White rabbits, placed in a Tyrode’s solution, and whole-cell patch clamped. They were exposed to 0-30nM ouabain, 0-50nM dihydroouabain (ouabain with a saturated lactone ring) or 0-500nM ouabagenin (ouabain lacking a sugar moiety) for 1 min, followed by a potassium-free solution, with the difference in current yielding the NKP current. Compared to the 0.47±0.05 pA/pF Tyrode’s solution control (n=11), 5nM ouabain significantly increased NKP current to 0.69±0.09 pA/pF ( P <0.05, n=6). Exposure to dihydroouabain or ouabagenin did not significantly change NKP current in the studied concentration range. Cell viability assays carried out on the breast cancer cell line MCF7, which have an NKP structure extremely similar to that of cardiomyocytes, showed significantly elevated viability above control values (n=2) following 24h treatment with 0-9nM ouabain; maximum viability was 116±5% at 0.28nM ( P <0.05, n=4). A significant change in viability was not observed for ouabagenin or digoxin in the same concentration range. Conclusion: Low-dose ouabain uniquely stimulates NKP activity. Low-dose dihydroouabain and ouabagenin do not, suggesting that a sugar moiety and unsaturated lactone ring are required for pump stimulation. Ouabain in its unaltered form may be a potential treatment for HF.

CARDIOTONIC ACTIVITY OF CERTAIN STEROIDS AND BILE SALTS

1952 ◽  
Vol 30 (4) ◽  
pp. 325-332 ◽  
Author(s):  
J. S. Loynes ◽  
C. W. Gowdey
Keyword(s):  
Heart Rate ◽  
Steroid Hormones ◽  
Coronary Flow ◽  
Bile Salts ◽  
Lactone Ring ◽  
Water Soluble ◽  
Force Of Contraction ◽  
Cardiotonic Activity ◽  
Cardiotonic Action ◽  
Significant Augmentation

The effects of 23 plant and animal steroids, steroid hormones, and bile acids, and nine of their salts or soluble conjugates, have been investigated in isolated frog hearts. All but five of the compounds produced significant augmentation of frog hearts made hypodynamic by prolonged perfusion. The augmentation was not usually accompanied by changes in heart rate, and no steroid caused systolic arrest. Eight water-soluble steroid salts were perfused through isolated rabbit hearts when they had become hypodynamic by prolonged perfusion. In each case the coronary flow increased significantly whether the heart rate and force of contraction increased or not. Thus, when cardiotonic activity was observed, it appeared to be a direct effect and not secondary to the increased coronary flow. It would seem that the lactone ring of the cardiac glycoside molecule is responsible for the development of systolic arrest, and that the cardiotonic action is, at least partly, a function of the cyclopentenophenanthrene nucleus.

FURTHER DEGRADATION REACTIONS OF ANNOTININE

1955 ◽  
Vol 33 (5) ◽  
pp. 849-860 ◽  
Author(s):  
F. A. L. Anet ◽  
Léo Marion
Keyword(s):  
Amino Acid ◽  
Benzene Ring ◽  
Potassium Permanganate ◽  
Lactone Ring ◽  
Neutral Substance ◽  
Unsaturated Lactone ◽  
Degradation Reactions ◽  
Vinyl Group ◽  
Color Reactions ◽  
Chromous Chloride

Both the hydroxylactone obtained by the action of chromous chloride on annotinine chlorohydrin, and the unsaturated lactone B prepared by the action of the same reagent on the hydroxylactone, contain a secondary nitrogen and a vinyl group. The unsaturated lactone A which accompanies the hydroxylactone is a cyclic allylamine which on oxidation with potassium permanganate yields an amino acid C14H19O4N. These facts make it possible to explain the reaction of chromous chloride with annotinine chlorohydrin. The amino acid can be de-hydrogenated to an acid containing a free carboxyl and a lactamic grouping (C14H15O3N) but no longer containing a lactone ring. The lactamic acid which seems to contain a benzene ring is readily decarboxylated to a neutral substance C13H15ON, showing color reactions and ultraviolet absorption similar to those of strychnine.

Research on unsaturated lactones. 49. Synthesis of thiazolidines that contain an ?,?-unsaturated ?-lactone ring

1981 ◽  
Vol 17 (4) ◽  
pp. 338-339
Author(s):  
A. N. Dzhandzhapanyan ◽  
A. A. Avetisyan ◽  
A. A. Oganesyan ◽  
M. T. Dangyan
Keyword(s):  
Lactone Ring ◽  
Unsaturated Lactone ◽  
Unsaturated Lactones

Reflections on the Cognitive Interviewing Reporting Framework

Methodology ◽  
2013 ◽  
Vol 9 (3) ◽  
pp. 123-128 ◽  
Author(s):  
Gordon Willis ◽  
Hennie Boeije
Keyword(s):  
Research Design ◽  
Cognitive Testing ◽  
Level Of Detail ◽  
Cognitive Interviewing ◽  
Research Groups ◽  
Research Project ◽  
Reporting Framework ◽  
Full Explanation ◽  
Key Steps

Based on the experiences of three research groups using and evaluating the Cognitive Interviewing Reporting Framework (CIRF), we draw conclusions about the utility of the CIRF as a guide to creating cognitive testing reports. Authors generally found the CIRF checklist to be usable, and that it led to a more complete description of key steps involved. However, despite the explicit direction by the CIRF to include a full explanation of major steps and features (e.g., research objectives and research design), the three cognitive testing reports tended to simply state what was done, without further justification. Authors varied in their judgments concerning whether the CIRF requires the appropriate level of detail. Overall, we believe that current cognitive interviewing practice will benefit from including, within cognitive testing reports, the 10 categories of information specified by the CIRF. Future use of the CIRF may serve to direct the overall research project from the start, and to further the goal of evaluation of specific cognitive interviewing procedures.

The development of alternative energy sources: Prospects in Russia and the world

2020 ◽  
Vol 16 (5) ◽  
pp. 885-904
Author(s):  
M.E. Frai
Keyword(s):  
Alternative Energy ◽  
Systems Approach ◽  
Energy Resource ◽  
Current Situation ◽  
Energy Sources ◽  
The Sustainable Development ◽  
Energy Complex ◽  
Alternative Energy Sources ◽  
Governmental Institutions ◽  
Key Steps

Subject. The article discusses limited sources of energy nowadays and an ongoing survey of new ones. I focus on fuel and energy complexes worldwide and in Russia. Objectives. The study is to analyze the future use of alternative energy sources in the fuel and energy complex nationwide and worldwide. I review the existing energy sources of the fuel and energy complex in the global and regional markets, specifically the alternative ones. Methods. The study relies upon methods of statistics, analysis and systems approach. Results. The article demonstrates that the fuel and energy complex strongly depends on the current situation in the energy resource market, which is difficult to forecast. If we continue relying on traditional energy resources, we get exposed to some risks affecting the sustainable development of the economy. Russia should diversify the power engineering sector by developing alternative energy sources. The article sets forth the economic rationale for alternative sources and key steps Russia shall make. Conclusions and Relevance. Considering the current situation in the energy balance, alternative energy is what any advanced society seeks for, being supported by manufacturers, governmental institutions, and researchers, though low profitability and high infrastructure costs impede its development. In Russia, these challenges are even more palpable. However, even now Russia is able to find alternative energy solutions. In addition to advantages of alternative energy, which is globally proclaimed, they will also help Russia diversify and update the economic system.

CO2 Activation on Heterostructures of Bi2O3-Nanocluster Modified TiO2: Promoting the Critical First Step in CO2 Conversion

2018 ◽  
Author(s):  
Michael Nolan
Keyword(s):  
Metal Oxide ◽  
Density Functional ◽  
Initial Step ◽  
Difficult Problem ◽  
Carbonate Formation ◽  
Structural Distortions ◽  
Strong Adsorption ◽  
Two Factors ◽  
Key Steps ◽  
Recent Experimental Work

The conversion of CO<sub>2</sub> to fuels is of significant importance in enabling the production of sustainable fuels, contributing to alleviating greenhouse gas emissions. While there are a number of key steps required to convert CO<sub>2</sub>, the initial step of adsorption and activation by the catalyst is critical. Well-known metal oxides such as oxidised TiO<sub>2</sub> or CeO<sub>2</sub> are unable to promote this step. In addressing this difficult problem, recent experimental work shows the potential for bismuth-containing materials to activate and convert CO<sub>2</sub>, but the origin of this activity is not yet clear. Additionally, nanostructures can show enhanced activity towards CO<sub>2</sub>. In this paper we present density functional theory (DFT) simulations of CO<sub>2</sub> activation on heterostructured materials composed of extended rutile and anatase TiO<sub>2</sub> surfaces modified with nanoclusters with Bi<sub>2</sub>O<sub>3</sub> stoichiometry. These heterostructures show low coordinated Bi sites in the nanoclusters and a valence band edge that is dominated by Bi-O states. These two factors mean that supported Bi<sub>2</sub>O<sub>3</sub> nanoclusters are able to adsorb and activate CO<sub>2</sub>. Computed adsorption energies lie in the range of -0.54 eV to -1.01 eV. In these strong adsorption modes, CO<sub>2</sub> is activated, in which the molecule bends giving O-C-O angles of 126 - 130<sup>o</sup> and elongation of C-O distances up to 1.28 Å, with no carbonate formation. The electronic properties show a strong CO<sub>2</sub>-Bi-oxygen interaction that drives the interaction of CO<sub>2</sub> to induce the structural distortions. Bi<sub>2</sub>O<sub>3</sub>-TiO<sub>2</sub> heterostructures can be reduced to form Bi<sup>2+</sup> and Ti<sup>3+</sup> species. The interaction of CO<sub>2</sub> with this electron-rich, reduced system can produce CO directly, reoxidising the heterostructure or form an activated carboxyl species (CO<sub>2</sub><sup>-</sup>) through electron transfer from the heterostructure to CO<sub>2</sub>. These results highlight that a semiconducting metal oxide modified with suitable metal oxide nanoclusters can activate CO<sub>2</sub>, thus overcoming the difficulties associated with the difficult first step in CO<sub>2</sub> conversion.

Phytochemical Evaluation and Screening of Cardiotonic, Antibacterial and Anthelmintic Activities of Sida cordifolia L.

2014 ◽  
Vol 7 (3) ◽  
pp. 2567-2573
Author(s):  
Sarella Prakash Nathaniel Kumar ◽  
Kanthal L.K. ◽  
Durga S ◽  
Achutha Rama Raju D ◽  
Satyavati K
Keyword(s):  
Antibacterial Activity ◽  
Rural Areas ◽  
Anthelmintic Activity ◽  
Diffusion Method ◽  
Frog Heart ◽  
Aqueous Extracts ◽  
Cardiotonic Activity ◽  
Herbal Products ◽  
High Antibacterial Activity ◽  
Sida Cordifolia

Several herbs are traditionally used in the treatment of a variety of ailments particularly in the rural areas, where herbal medicine is mainly the source of health care system. Many of these herbs havenot been assessed for safety or toxicity to tissue or organs of the mammalian recipients. An attempt is made to prove the efficacy of Sida cordifolia Linn., (a traditional medicinal plant chosen on the basis of ethnomedical knowledge) for its Cardiotonic, Antibacterial and Anthelmintic activities. Sida cordofolia Linn., is used traditionally, inter alia, in the treatment of various infections, asthma, diarrhoea, heart and stomach disorders. Cardiotonicactivity is performed using isolated Frog Heart Perfusion Technique. Antibacterial activity of the whole plant extracts were assessed by Agar well diffusion method against the strains of Bacillus subtilis, Escherichia coli, and Staphylococcus aureus. Anthelmintic activity was studied against Pheretima posthuma. Phytochemical screening of powdered plant material revealed thepresence of some secondary metabolites such as alkaloids, saponins, tannins, glycosides and flavonoids. Results indicated that methanol, chloroform, aqueous extracts have significant cardiotonic activity but less than standard drugs. Methanol and Aqueous extracts showed high antibacterial activity and anthelmintic activity than the standard drugs. In a nutshell, we can conclude that the methanol and aqueous fractions of Sida cordifolia Linn., had a profound antibacterial and anthelmintic effect eventhough it possessed very significant cardiotonic activity. This validates its continuous usage in ethnomedicine. This plant could be developed into cheap, safe and culturally acceptable standardized herbal products and may serve as asource of new molecules for broad-spectrum antimicrobial and anthelmintic agent.

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