The Experts below are selected from a list of 48846 Experts worldwide ranked by ideXlab platform

Alex S Kiselyov - One of the best experts on this subject based on the ideXlab platform.

  • polyalkoxybenzenes from plants 5 parsley seed extract in synthesis of azapodophyllotoxins featuring strong tubulin destabilizing activity in the sea urchin embryo and Cell Culture Assays
    Journal of Medicinal Chemistry, 2011
    Co-Authors: Marina N Semenova, Alex S Kiselyov, Mikhail M Raihstat, Dmitry V Tsyganov, L D Konyushkin, S I Firgang, Roman V Semenov, Oleg R Malyshev, Fabian Fuchs, Anne Stielow
    Abstract:

    A series of 4-azapodophyllotoxin derivatives with modified rings B and E have been synthesized using allylpolyalkoxybenzenes from parsley seed oil. The targeted molecules were evaluated in vivo in a phenotypic sea urchin embryo assay for antimitotic and tubulin destabilizing activity. The most active compounds identified by the in vivo sea urchin embryo assay featured myristicin-derived ring E (4e, 6e, and 8e). These molecules were determined to be more potent than podophyllotoxin. Cytotoxic effects of selected molecules were further confirmed and evaluated by conventional Assays with A549 and Jurkat human leukemic T-Cell lines including Cell growth inhibition, Cell cycle arrest, Cellular microtubule disruption, and induction of apoptosis. The ring B modification yielded 6-OMe substituted molecule 8e as the most active compound. Finally, in Jurkat Cells, compound 8e induced caspase-dependent apoptosis mediated by the apical caspases-2 and -9 and not caspase-8, implying the involvement of the intrinsic cas...

  • novel derivatives of 1 3 4 oxadiazoles are potent mitostatic agents featuring strong microtubule depolymerization activity in the sea urchin embryo and Cell Culture Assays
    ChemInform, 2010
    Co-Authors: Alex S Kiselyov
    Abstract:

    The synthesis of a limited number of novel isothiazolyl-substituted 1,3,4-oxadiazoles (V) is described.

  • novel derivatives of 1 3 4 oxadiazoles are potent mitostatic agents featuring strong microtubule depolymerizing activity in the sea urchin embryo and Cell Culture Assays
    European Journal of Medicinal Chemistry, 2010
    Co-Authors: Alex S Kiselyov, Marina N Semenova, Natalya B Chernyshova, Andrei Leitao, Alexandr V Samet, Konstantine A Kislyi, Mikhail M Raihstat, Tudor I Oprea, Heiko Lemcke, Margareta Lantow
    Abstract:

    Abstract A series of novel 1,3,4-oxadiazole derivatives based on structural and electronic overlap with combretastatins have been designed and synthesized. Initially, we tested all new compounds in vivo using the phenotypic sea urchin embryo assay to yield a number of agents with anti-proliferative, anti-mitotic, and microtubule destabilizing activities. The experimental data led to identification of 1,3,4-oxadiazole derivatives with isothiazole ( 5 – 8 ) and phenyl ( 9 – 12 ) pharmacophores featuring activity profiles comparable to that of combretastatins, podophyllotoxin and nocodazole. Cytotoxic effects of the two lead molecules, namely 6 and 12 , were further confirmed and evaluated by conventional Assays with the A549 human cancer Cell line including Cell proliferation, Cell cycle arrest at the G2/M phase, Cellular microtubule distribution, and finally in vitro microtubule assembly with purified tubulin. The modeling results using 3D similarity (ROCS) and docking (FRED) correlated well with the observed activity of the molecules. Docking data suggested that the most potent molecules are likely to target the colchicine binding site.

Harriet B. Taylor - One of the best experts on this subject based on the ideXlab platform.

  • Cell segregation and border sharpening by eph receptor ephrin mediated heterotypic repulsion
    Journal of the Royal Society Interface, 2017
    Co-Authors: Harriet B. Taylor, Anaïs Khuong, Rosalind Morley, Lauren Gregory, Alexei Poliakov, William R. Taylor, David G. Wilkinson
    Abstract:

    Eph receptor and ephrin signalling has a major role in Cell segregation and border formation, and may act through regulation of Cell adhesion, repulsion or tension. To elucidate roles of Cell repulsion and adhesion, we combined experiments in Cell Culture Assays with quantitations of Cell behaviour which are used in computer simulations. Cells expressing EphB2, or kinase-inactive EphB2 (kiEphB2), segregate and form a sharp border with ephrinB1-expressing Cells, and this is disrupted by knockdown of N-cadherin. Measurements of contact inhibition of locomotion reveal that EphB2-, kiEphB2- and ephrinB1-expressing Cells have strong heterotypic and weak homotypic repulsion. EphB2 Cells have a transient increase in migration after heterotypic activation, which underlies a shift in the EphB2-ephrinB1 border but is not required for segregation or border sharpening. Simulations with the measured values of Cell behaviour reveal that heterotypic repulsion can account for Cell segregation and border sharpening, and is more efficient than decreased heterotypic adhesion. By suppressing homotypic repulsion, N-cadherin creates a sufficient difference between heterotypic and homotypic repulsion, and enables homotypic cohesion, both of which are required to sharpen borders.

  • Movie 2 from Cell segregation and border sharpening by Eph receptor: ephrin-mediated heterotypic repulsion
    2017
    Co-Authors: Harriet B. Taylor, Anaïs Khuong, Rosalind Morley, Lauren Gregory, Alexei Poliakov, William R. Taylor, David G. Wilkinson
    Abstract:

    Eph receptor and ephrin signalling has a major role in Cell segregation and border formation, and may act through regulation of Cell adhesion, repulsion or tension. To elucidate roles of Cell repulsion and adhesion, we combined experiments in Cell Culture Assays with quantitations of Cell behaviour which are used in computer simulations. Cells expressing EphB2, or kinase-inactive EphB2 (kiEphB2), segregate and form a sharp border with ephrinB1-expressing Cells, and this is disrupted by knockdown of N-cadherin. Measurements of contact inhibition of locomotion reveal that EphB2-, kiEphB2- and ephrinB1-expressing Cells have strong heterotypic and weak homotypic repulsion. EphB2 Cells have a transient increase in migration after heterotypic activation, which underlies a shift in the EphB2–ephrinB1 border but is not required for segregation or border sharpening. Simulations with the measured values of Cell behaviour reveal that heterotypic repulsion can account for Cell segregation and border sharpening, and is more efficient than decreased heterotypic adhesion. By suppressing homotypic repulsion, N-cadherin creates a sufficient difference between heterotypic and homotypic repulsion, and enables homotypic cohesion, both of which are required to sharpen borders

  • Captions for movies and Suppl. Figs from Cell segregation and border sharpening by Eph receptor: ephrin-mediated heterotypic repulsion
    2017
    Co-Authors: Harriet B. Taylor, Anaïs Khuong, Rosalind Morley, Lauren Gregory, Alexei Poliakov, William R. Taylor, David G. Wilkinson
    Abstract:

    Eph receptor and ephrin signalling has a major role in Cell segregation and border formation, and may act through regulation of Cell adhesion, repulsion or tension. To elucidate roles of Cell repulsion and adhesion, we combined experiments in Cell Culture Assays with quantitations of Cell behaviour which are used in computer simulations. Cells expressing EphB2, or kinase-inactive EphB2 (kiEphB2), segregate and form a sharp border with ephrinB1-expressing Cells, and this is disrupted by knockdown of N-cadherin. Measurements of contact inhibition of locomotion reveal that EphB2-, kiEphB2- and ephrinB1-expressing Cells have strong heterotypic and weak homotypic repulsion. EphB2 Cells have a transient increase in migration after heterotypic activation, which underlies a shift in the EphB2–ephrinB1 border but is not required for segregation or border sharpening. Simulations with the measured values of Cell behaviour reveal that heterotypic repulsion can account for Cell segregation and border sharpening, and is more efficient than decreased heterotypic adhesion. By suppressing homotypic repulsion, N-cadherin creates a sufficient difference between heterotypic and homotypic repulsion, and enables homotypic cohesion, both of which are required to sharpen borders

Margareta Lantow - One of the best experts on this subject based on the ideXlab platform.

  • novel derivatives of 1 3 4 oxadiazoles are potent mitostatic agents featuring strong microtubule depolymerizing activity in the sea urchin embryo and Cell Culture Assays
    European Journal of Medicinal Chemistry, 2010
    Co-Authors: Alex S Kiselyov, Marina N Semenova, Natalya B Chernyshova, Andrei Leitao, Alexandr V Samet, Konstantine A Kislyi, Mikhail M Raihstat, Tudor I Oprea, Heiko Lemcke, Margareta Lantow
    Abstract:

    Abstract A series of novel 1,3,4-oxadiazole derivatives based on structural and electronic overlap with combretastatins have been designed and synthesized. Initially, we tested all new compounds in vivo using the phenotypic sea urchin embryo assay to yield a number of agents with anti-proliferative, anti-mitotic, and microtubule destabilizing activities. The experimental data led to identification of 1,3,4-oxadiazole derivatives with isothiazole ( 5 – 8 ) and phenyl ( 9 – 12 ) pharmacophores featuring activity profiles comparable to that of combretastatins, podophyllotoxin and nocodazole. Cytotoxic effects of the two lead molecules, namely 6 and 12 , were further confirmed and evaluated by conventional Assays with the A549 human cancer Cell line including Cell proliferation, Cell cycle arrest at the G2/M phase, Cellular microtubule distribution, and finally in vitro microtubule assembly with purified tubulin. The modeling results using 3D similarity (ROCS) and docking (FRED) correlated well with the observed activity of the molecules. Docking data suggested that the most potent molecules are likely to target the colchicine binding site.

David G. Wilkinson - One of the best experts on this subject based on the ideXlab platform.

  • Cell segregation and border sharpening by eph receptor ephrin mediated heterotypic repulsion
    Journal of the Royal Society Interface, 2017
    Co-Authors: Harriet B. Taylor, Anaïs Khuong, Rosalind Morley, Lauren Gregory, Alexei Poliakov, William R. Taylor, David G. Wilkinson
    Abstract:

    Eph receptor and ephrin signalling has a major role in Cell segregation and border formation, and may act through regulation of Cell adhesion, repulsion or tension. To elucidate roles of Cell repulsion and adhesion, we combined experiments in Cell Culture Assays with quantitations of Cell behaviour which are used in computer simulations. Cells expressing EphB2, or kinase-inactive EphB2 (kiEphB2), segregate and form a sharp border with ephrinB1-expressing Cells, and this is disrupted by knockdown of N-cadherin. Measurements of contact inhibition of locomotion reveal that EphB2-, kiEphB2- and ephrinB1-expressing Cells have strong heterotypic and weak homotypic repulsion. EphB2 Cells have a transient increase in migration after heterotypic activation, which underlies a shift in the EphB2-ephrinB1 border but is not required for segregation or border sharpening. Simulations with the measured values of Cell behaviour reveal that heterotypic repulsion can account for Cell segregation and border sharpening, and is more efficient than decreased heterotypic adhesion. By suppressing homotypic repulsion, N-cadherin creates a sufficient difference between heterotypic and homotypic repulsion, and enables homotypic cohesion, both of which are required to sharpen borders.

  • Movie 2 from Cell segregation and border sharpening by Eph receptor: ephrin-mediated heterotypic repulsion
    2017
    Co-Authors: Harriet B. Taylor, Anaïs Khuong, Rosalind Morley, Lauren Gregory, Alexei Poliakov, William R. Taylor, David G. Wilkinson
    Abstract:

    Eph receptor and ephrin signalling has a major role in Cell segregation and border formation, and may act through regulation of Cell adhesion, repulsion or tension. To elucidate roles of Cell repulsion and adhesion, we combined experiments in Cell Culture Assays with quantitations of Cell behaviour which are used in computer simulations. Cells expressing EphB2, or kinase-inactive EphB2 (kiEphB2), segregate and form a sharp border with ephrinB1-expressing Cells, and this is disrupted by knockdown of N-cadherin. Measurements of contact inhibition of locomotion reveal that EphB2-, kiEphB2- and ephrinB1-expressing Cells have strong heterotypic and weak homotypic repulsion. EphB2 Cells have a transient increase in migration after heterotypic activation, which underlies a shift in the EphB2–ephrinB1 border but is not required for segregation or border sharpening. Simulations with the measured values of Cell behaviour reveal that heterotypic repulsion can account for Cell segregation and border sharpening, and is more efficient than decreased heterotypic adhesion. By suppressing homotypic repulsion, N-cadherin creates a sufficient difference between heterotypic and homotypic repulsion, and enables homotypic cohesion, both of which are required to sharpen borders

  • Captions for movies and Suppl. Figs from Cell segregation and border sharpening by Eph receptor: ephrin-mediated heterotypic repulsion
    2017
    Co-Authors: Harriet B. Taylor, Anaïs Khuong, Rosalind Morley, Lauren Gregory, Alexei Poliakov, William R. Taylor, David G. Wilkinson
    Abstract:

    Eph receptor and ephrin signalling has a major role in Cell segregation and border formation, and may act through regulation of Cell adhesion, repulsion or tension. To elucidate roles of Cell repulsion and adhesion, we combined experiments in Cell Culture Assays with quantitations of Cell behaviour which are used in computer simulations. Cells expressing EphB2, or kinase-inactive EphB2 (kiEphB2), segregate and form a sharp border with ephrinB1-expressing Cells, and this is disrupted by knockdown of N-cadherin. Measurements of contact inhibition of locomotion reveal that EphB2-, kiEphB2- and ephrinB1-expressing Cells have strong heterotypic and weak homotypic repulsion. EphB2 Cells have a transient increase in migration after heterotypic activation, which underlies a shift in the EphB2–ephrinB1 border but is not required for segregation or border sharpening. Simulations with the measured values of Cell behaviour reveal that heterotypic repulsion can account for Cell segregation and border sharpening, and is more efficient than decreased heterotypic adhesion. By suppressing homotypic repulsion, N-cadherin creates a sufficient difference between heterotypic and homotypic repulsion, and enables homotypic cohesion, both of which are required to sharpen borders

David M Yourtee - One of the best experts on this subject based on the ideXlab platform.

  • lipid vesicles as membrane models for toxicological assessment of xenobiotics
    Critical Reviews in Toxicology, 2008
    Co-Authors: Helmut H Zepik, Peter Walde, Elisabet L Kostoryz, Jim Code, David M Yourtee
    Abstract:

    Traditionally animals and Cell Cultures have been used to assess the toxic potential of xenobiotics on Cell membranes. In search for more reproducible, quantitative, cost- and time-effective Assays, toxicologists have recently become interested in biomimetic lipid vesicle-based test systems. Lipid vesicles (liposomes) have long been appreciated as simple Cell membrane models in biochemical and biophysical studies providing a good understanding of the physicochemical properties of liposome systems. More recently a number of reports have been published on the interactions of toxic substances with vesicles. Literature reports on liposome Assays have appeared for widely different classes of xenobiotics, such as dental materials, antibiotics, detergents, and peptides. In this review we focus on those reports that contain a quantitative and significant correlation with more established toxicological tests like Cell Culture Assays. We provide an introduction to the structure and main characteristics of vesicles ...

  • lipid vesicles as membrane models for toxicological assessment of xenobiotics
    Critical Reviews in Toxicology, 2008
    Co-Authors: Helmut H Zepik, Peter Walde, Elisabet L Kostoryz, Jim Code, David M Yourtee
    Abstract:

    Traditionally animals and Cell Cultures have been used to assess the toxic potential of xenobiotics on Cell membranes. In search for more reproducible, quantitative, cost- and time-effective Assays, toxicologists have recently become interested in biomimetic lipid vesicle-based test systems. Lipid vesicles (liposomes) have long been appreciated as simple Cell membrane models in biochemical and biophysical studies providing a good understanding of the physicochemical properties of liposome systems. More recently a number of reports have been published on the interactions of toxic substances with vesicles. Literature reports on liposome Assays have appeared for widely different classes of xenobiotics, such as dental materials, antibiotics, detergents, and peptides. In this review we focus on those reports that contain a quantitative and significant correlation with more established toxicological tests like Cell Culture Assays. We provide an introduction to the structure and main characteristics of vesicles and related lipid aggregates. The two main Assays presented are leakage of fluorescence dyes and differential scanning calorimetry (DSC) measurements of the solid-ordered/liquid-disordered main phase transition temperature (Tm).