<strong>Lead Selection of Antiparasitic Compounds from a Focused Library of Benzenesulfonyl Derivatives of Heterocycles</strong>

N,N-Dialkyl derivatives of 3-aminoisoquinoline have been prepared by reaction of nitriles with various arylacetic acid tertiary amides in the presence of phosphoryl chloride. The synthesis has been extended to include a benzoisoquinoline and annulated isoquinolines by the selection of appropriate amide and nitrile precursors.

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New computational studies to support cyclin-dependent kinase 9 inhibitor screening and design

Acta Pharmaceutica Hungarica ◽

10.33892/aph.2019.89.31-38 ◽

2019 ◽

Vol 89 (1) ◽

pp. 31-38

Author(s):

Márk Fábián ◽

Balázs Balogh ◽

Zsófia Czudor ◽

László Őrfi

Keyword(s):

Qsar Model ◽

Regulation Of Transcription ◽

Computational Studies ◽

Cyclin Dependent Kinase ◽

Active Compounds ◽

Target Interaction ◽

Antiapoptotic Proteins ◽

Lead Selection ◽

Pharmacophore Hypothesis ◽

Selection Of

Aims: Cyclin-dependent kinase 9 (CDK9) plays a major role in the regulation of transcription. Its overexpression -which occurs in several types of cancer- increases the levels of certain antiapoptotic proteins that can lead to tumorigenesis, therefore the identification of new, more potent and more selective inhibitors is essential. Methods: In this study we present a computational approach, which can facilitate lead selection and optimization. Results: First, a pharmacophore hypothesis based on the active compounds has been developed to identify the key features for the ligand-target interaction. This was followed by the docking of the compounds into the active site of CDK9, the poses and interactions with the amino acids were compared with those of the co-crystallized ligand. The mode of their binding further explained the characteristics of these inhibitors while the docking scores can be a factor in the selection of active compounds in the future. Finally, a field-based QSAR model was also created, to predict the activity of inhibitor candidates. Conclusion: With our current work we deepened our knowledge about the interactions between CDK9 and its inhibitors, which can contribute to the discovery of novel CDK9 inhibitors.

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Effective photosensibilizator selection for e.n.t.-organ diseases treatment, based on their accumulation in pathologically changed tissues

Biomeditsinskaya Khimiya ◽

10.18097/pbmc20125801112 ◽

2012 ◽

Vol 58 (1) ◽

pp. 112-120 ◽

Cited By ~ 3

Author(s):

Y.V. Alexeev ◽

E.V. Likhacheva ◽

D.V. Tereshkin ◽

G.V. Ponomarev ◽

E.M. Mazur

Keyword(s):

Mucous Membrane ◽

Light Emitting Diode ◽

Clinical Results ◽

Therapeutic Activity ◽

Laser Device ◽

Light Emitting ◽

Selection For ◽

Derivatives Of ◽

Led Matrix ◽

Selection Of

Accumulation of photosensibilisators - derivatives of E6 chlorines ("Radachlorine", "Photoditazine", "Zelevsky's balsam") in the mucous membrane and selection of most effective sources of emission have been investigated in 30 patients with rhinosinusitis and 10 with tonsillitis. As a source of emission we used light emitting diode (LED) matrix device "ACT" (wavelength approximately 405 nm (Sore band)) and a laser device LAHTA-"MILON"-ML500-SP (wavelength - 662 nm). Drug accumulation in the mucous membrane and changes of their concentrations after emission were evaluated by changes of fluorescence, measured with a LESA-01-BIOSPEC spectrometer. The percent of fluorescence decrease ranged from 50% to 92.7%. This suggests intensive disintegration of photosensibilisators, and consequently, high therapeutic activity of this method. Effectiveness of this method is also confirmed by clinical results.

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Screening for Cardiovascular Safety: A Structure−Activity Approach for Guiding Lead Selection of Melanin Concentrating Hormone Receptor 1 Antagonists

Journal of Medicinal Chemistry ◽

10.1021/jm0512286 ◽

2006 ◽

Vol 49 (7) ◽

pp. 2339-2352 ◽

Cited By ~ 22

Author(s):

Philip R. Kym ◽

Andrew J. Souers ◽

Thomas J. Campbell ◽

John K. Lynch ◽

Andrew S. Judd ◽

...

Keyword(s):

Hormone Receptor ◽

Cardiovascular Safety ◽

Structure Activity ◽

Lead Selection ◽

Melanin Concentrating Hormone ◽

Selection Of

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Emergence of Biofilm-Forming Subpopulations upon Exposure of Escherichia coli to Environmental Bacteriophages

Applied and Environmental Microbiology ◽

10.1128/aem.72.1.956-959.2006 ◽

2006 ◽

Vol 72 (1) ◽

pp. 956-959 ◽

Cited By ~ 41

Author(s):

Andrea Lacqua ◽

Oskar Wanner ◽

Teresa Colangelo ◽

Maria Giovanna Martinotti ◽

Paolo Landini

Keyword(s):

Escherichia Coli ◽

Membrane Protein ◽

Outer Membrane ◽

Outer Membrane Protein ◽

Biofilm Formation ◽

Type I ◽

Selection For ◽

Dps Protein ◽

Derivatives Of ◽

Selection Of

ABSTRACT Exposure of Escherichia coli MG1655 to environmental bacteriophages results in rapid selection for phage-tolerant subpopulations displaying increased biofilm formation. Analysis of one phage-tolerant strain revealed large amounts of the DNA-binding Dps protein in the outer membrane protein and production of fimbria-like structures. In dps and fimA mutant derivatives of MG1655, no selection of phage-tolerant bacteria upon exposure to bacteriophages occurred, suggesting a role for Dps and type I pili in bacteriophage tolerance.

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Anatomo-histological structure of inner sexual organs of goats of Zaanenskaya breed Application of derivatives of incomplete wheat-wild-rye amphiploid (WWRA) Elytricum fertile in selection of winter soft wheat

Visnyk agrarnoi nauky ◽

10.31073/agrovisnyk201708-07 ◽

2017 ◽

Vol 95 (8) ◽

pp. 41-44

Author(s):

S. Demchuk ◽

K. Skoryk

Keyword(s):

Soft Wheat ◽

Histological Structure ◽

Derivatives Of ◽

Selection Of

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Word-formation motivation as a means of lexicalizing derivative words in the classroom in Russian as a foreign language

World of Science Pedagogy and psychology ◽

10.15862/19pdmn221 ◽

2021 ◽

Vol 9 (2) ◽

Author(s):

Elena Demidova

Keyword(s):

Foreign Language ◽

Foreign Students ◽

Communicative Competence ◽

Word Formation ◽

Russian Language ◽

Holistic View ◽

Generating Relations ◽

Systemic Understanding ◽

Derivatives Of ◽

Selection Of

The article examines the place of the word-formation component of the communicative competence of foreign students in the process of their learning Russian as a foreign language. The word-formation component, along with other linguistic components, participates in the formation of the communicative competence of foreign students, however, the problem of Russian word formation remains insufficiently developed in the linguodidactic plan. The author expresses his opinion that the increase in the vocabulary of foreign students should be accompanied by the systematization of lexical units, taking into account their derivational connections and relations. Therefore, when lexicalization, one should use not the selection of synonyms or the descriptive method, which leads to the mechanical memorization of the meaning, but by means of correlation with the same root words, to activate in the minds of foreign students the living connections of the lexical units of the Russian language. This applies not only to derivatives of words associated with generating relations of full direct motivation, but also to those derivatives where these connections are not explicitly expressed. Such an interpretation through a productive word not only makes the meaning of the new lexeme understandable, facilitates its memorization, but also creates a single picture of lexical and word-formation relationships within the language, forms a systemic understanding of the language among students. The skills of correlating a derivative word with its derivative, obtained in the study of Russian as a foreign language, make it possible to understand the meanings of unfamiliar words. The speed of memorizing the meanings of derived words in this case directly depends on the understanding of the word-formation structure of the word. This technique will greatly facilitate the development of the vocabulary and will contribute to the formation of a holistic view of the language as a system among foreign students.

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Estimation of the integral of the square of derivatives of symmetric probability densities of one-dimensional random variables

Metrologiya ◽

10.32446/0132-4713.2020-1-15-27 ◽

2020 ◽

pp. 15-27

Author(s):

Aleksandr V. Lapko ◽

Vasiliy A. Lapko

Keyword(s):

Standard Deviation ◽

Probability Density ◽

Random Variables ◽

Random Variable ◽

Density Estimates ◽

One Dimensional ◽

Probability Densities ◽

The One ◽

Derivatives Of ◽

Selection Of

When substantiating the method of fast selection of the bandwidth of kernel probability density estimates, a constant was found that is a functional of the second density derivative. In this paper, the obtained result is generalized to derivatives of symmetric probability densities of different orders. The functional dependences of the constants under study on the coeffi cient of antikurtosis of a random variable are established. The regularities peculiar to them are investigated. Based on the results obtained, a method for estimating functionals from derived probability densities has been developed, which involves the following actions. In the original sample estimated standard deviation of the one-dimensional random variables and the coeffi cient of antikurtosis. Using the reconstructed functional dependences on the antikurtosis coeffi cient, the constants are estimated, which are functionals of the derivatives of the probability density. With known estimates of the standard deviation of the investigated random variable and the considered constant, the values of the functional from the derivative of the probability density of the selected order are calculated. The obtained results are confi rmed by the analysis of the data of computational experiments. It is established that with increasing order of the derivative, the values of the estimates of the studied functionals increase. This fact is explained by the complication of the integrand function in the considered functionals. The proposed method provides objective results for the fi rst three derivatives of the probability density of a random variable. The obtained conclusions are confi rmed by the results of the confi dence estimation of the investigated functionals.

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The Analysis of Malignancy by Cell Fusion

Journal of Cell Science ◽

10.1242/jcs.8.3.659 ◽

1971 ◽

Vol 8 (3) ◽

pp. 659-672

Author(s):

G. KLEIN ◽

U. BREGULA ◽

F. WIENER ◽

H. HARRIS

Keyword(s):

Cell Line ◽

Tumour Cell ◽

Malignant Cell ◽

Hybrid Cells ◽

Metabolic Defects ◽

L Cell ◽

Wide Range ◽

Derivatives Of ◽

Selection Of

A wide range of different kinds of malignant cell were fused with certain derivatives of the L cell line and the ability of the resulting hybrid cells to grow progressively in vivo was examined. In all cases the highly malignant character of the tumour cells was suppressed by fusion with the L cell derivatives, whether or not these had metabolic defects that facilitated selection of the hybrid cells. So long as the hybrid cells retained the complete chromosome complements of the two parent cells, their ability to grow progressively in vivo was very limited, for tumours composed of such unreduced hybrids were not found. However, when they lost certain specific, but as yet unidentified, chromosomes, the hybrid cells regained the ability to grow progressively in vivo and gave rise to a tumour. These findings thus indicated that the L cell derivatives contributed something to the hybrid that suppressed the malignancy of the tumour cell, and that this contribution was lost when certain specific chromosomes were eliminated.

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