The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Masahiko Idei - One of the best experts on this subject based on the ideXlab platform.
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Lipophilicity of substituted aurones and related compounds measured on immobilized artificial membrane iam and conventional c8 mos columns
Journal of Liquid Chromatography & Related Technologies, 2008Co-Authors: Monika Huszar, Balazs Hallgas, Attila Kissszikszai, Anikó Horváth, Masahiko Idei, Tamas PatonayAbstract:Abstract A high performance liquid chromatographic method utilizing an immobilized artificial membrane (IAM HPLC) column has been developed to separate the members of a library containing 38 aurone and thioaurone type structures and to characterise their Lipophilicity. The experimental Lipophilicity data (k′IAM) have been compared with the previously determined ones C8(MOS) column (k′MOS) and with their calculated Lipophilicity parameters (CLOGP). In general, good correlations between the measured and calculated lipophilicities have been found both for the IAM and MOS column. The IAM column showed higher efficiency in separation of isomeric aurones or thioaurones than the MOS one and, consequently, it showed higher potential in differentiation of their lipophilicities. Our findings proved the usefulness of the HPLC method in fast characterisation of the Lipophilicity of drug candidates closely related in structure.
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Lipophilicity and antiproliferative activity profiling of 2-benzylidencycloalkanones.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2007Co-Authors: Balazs Hallgas, Masahiko Idei, Gy. Kéri, Zsófia Dobos, Attila Agócs, Tamás Loránd, György MészárosAbstract:High performance liquid chromatographic (HPLC) method has been developed to separate the members of a library including 24 benzylidenecycloalkanone-type structures and to characterize their Lipophilicity. The experimental Lipophilicity data (k) of the compounds have been compared with their calculated Lipophilicity parameters (CLOGP). In general, good correlations between the measured and calculated lipophilicities have been found and these results were in good accordance with our previously data obtained in case of structurally related molecular libraries. In addition, cytotoxicity screening has been performed to determine the antiproliferative activity of these compounds. Some of the investigated compounds possessed noticeable inhibitory potential. Based on the correlation between the antiproliferative activity and experimentally determined Lipophilicity of the molecules investigated, limited structural demands to obtain more potent compounds can be exhibited to support the synthetic design.
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Comparison of measured and calculated Lipophilicity of substituted aurones and related compounds
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2004Co-Authors: Balazs Hallgas, Tamas Patonay, Attila Kiss-szikszai, Zs Dobos, Ferenc Hollósy, Dániel Erős, László Őrfi, Gy. Kéri, Masahiko IdeiAbstract:A molecule library containing 55 aurone- and thioaurone-type structures has been designed and synthesised. Reversed phase high performance liquid chromatographic (RP-HPLC) method has been developed to separate these compounds and to characterise their Lipophilicity by experimental method (k'). The experimental Lipophilicity data have been compared with the computer calculated Lipophilicity parameters (CLOGPs) of the same molecules. In general, good correlations between the measured and calculated lipophilicities have been found with the exception of structure isomers and compounds capable for hydrogen bonding. The chromatographic method was suitable to separate the structure (ortho and para) isomers of aurone and thioaurones and was sensitive enough to differentiate their lipophilicities. Our findings suggest the usefulness of the chromatographic method in fast characterisation of the Lipophilicity of structurally closely related molecules.
Balazs Hallgas - One of the best experts on this subject based on the ideXlab platform.
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Lipophilicity of substituted aurones and related compounds measured on immobilized artificial membrane iam and conventional c8 mos columns
Journal of Liquid Chromatography & Related Technologies, 2008Co-Authors: Monika Huszar, Balazs Hallgas, Attila Kissszikszai, Anikó Horváth, Masahiko Idei, Tamas PatonayAbstract:Abstract A high performance liquid chromatographic method utilizing an immobilized artificial membrane (IAM HPLC) column has been developed to separate the members of a library containing 38 aurone and thioaurone type structures and to characterise their Lipophilicity. The experimental Lipophilicity data (k′IAM) have been compared with the previously determined ones C8(MOS) column (k′MOS) and with their calculated Lipophilicity parameters (CLOGP). In general, good correlations between the measured and calculated lipophilicities have been found both for the IAM and MOS column. The IAM column showed higher efficiency in separation of isomeric aurones or thioaurones than the MOS one and, consequently, it showed higher potential in differentiation of their lipophilicities. Our findings proved the usefulness of the HPLC method in fast characterisation of the Lipophilicity of drug candidates closely related in structure.
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Lipophilicity and antiproliferative activity profiling of 2-benzylidencycloalkanones.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2007Co-Authors: Balazs Hallgas, Masahiko Idei, Gy. Kéri, Zsófia Dobos, Attila Agócs, Tamás Loránd, György MészárosAbstract:High performance liquid chromatographic (HPLC) method has been developed to separate the members of a library including 24 benzylidenecycloalkanone-type structures and to characterize their Lipophilicity. The experimental Lipophilicity data (k) of the compounds have been compared with their calculated Lipophilicity parameters (CLOGP). In general, good correlations between the measured and calculated lipophilicities have been found and these results were in good accordance with our previously data obtained in case of structurally related molecular libraries. In addition, cytotoxicity screening has been performed to determine the antiproliferative activity of these compounds. Some of the investigated compounds possessed noticeable inhibitory potential. Based on the correlation between the antiproliferative activity and experimentally determined Lipophilicity of the molecules investigated, limited structural demands to obtain more potent compounds can be exhibited to support the synthetic design.
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Comparison of measured and calculated Lipophilicity of substituted aurones and related compounds
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2004Co-Authors: Balazs Hallgas, Tamas Patonay, Attila Kiss-szikszai, Zs Dobos, Ferenc Hollósy, Dániel Erős, László Őrfi, Gy. Kéri, Masahiko IdeiAbstract:A molecule library containing 55 aurone- and thioaurone-type structures has been designed and synthesised. Reversed phase high performance liquid chromatographic (RP-HPLC) method has been developed to separate these compounds and to characterise their Lipophilicity by experimental method (k'). The experimental Lipophilicity data have been compared with the computer calculated Lipophilicity parameters (CLOGPs) of the same molecules. In general, good correlations between the measured and calculated lipophilicities have been found with the exception of structure isomers and compounds capable for hydrogen bonding. The chromatographic method was suitable to separate the structure (ortho and para) isomers of aurone and thioaurones and was sensitive enough to differentiate their lipophilicities. Our findings suggest the usefulness of the chromatographic method in fast characterisation of the Lipophilicity of structurally closely related molecules.
Bernard Testa - One of the best experts on this subject based on the ideXlab platform.
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Lipophilicity and Its Relationship with Passive Drug Permeation
Pharmaceutical Research, 2011Co-Authors: Xiangli Liu, Bernard Testa, Alfred FahrAbstract:ABSTRACTIn this review, we first summarize the structure and properties of biological membranes and the routes of passive drug transfer through physiological barriers. Lipophilicity is then introduced in terms of the intermolecular interactions it encodes. Finally, Lipophilicity indices from isotropic solvent systems and from anisotropic membrane-like systems are discussed for their capacity to predict passive drug permeation across biological membranes such as the intestinal epithelium, the blood-brain barrier (BBB) or the skin. The broad evidence presented here shows that beyond the predictive power of Lipophilicity parameters, the various intermolecular forces they encode allow a mechanistic interpretation of passive drug permeation.
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liposome water Lipophilicity methods information content and pharmaceutical applications
Medicinal Research Reviews, 2004Co-Authors: Georgette Plemper Van Balen, Giulia Caron, Marianne Reist, Pierre-alain Carrupt, Géraldine Bouchard, Catherine Marca A Martinet, Roberta Fruttero, Alberto Gasco, Bernard TestaAbstract:This review discusses liposome/water Lipophilicity in terms of the structure of liposomes, experimental methods, and information content. In a first part, the structural properties of the hydrophobic core and polar surface of liposomes are examined in the light of potential interactions with solute molecules. Particular emphasis is placed on the physicochemical properties of polar headgroups of lipids in liposomes. A second part is dedicated to three useful methods to study liposome/water partitioning, namely potentiometry, equilibrium dialysis, and (1)H-NMR relaxation rates. In each case, the principle and limitations of the method are discussed. The next part presents the structural information encoded in liposome/water Lipophilicity, in other words the solutes' structural and physicochemical properties that determine their behavior and hence their partitioning in such systems. This presentation is based on a comparison between isotropic (i.e., solvent/water) and anisotropic (e.g., liposome/water) systems. An important factor to be considered is whether the anisotropic lipid phase is ionized or not. Three examples taken from the authors' laboratories are discussed to illustrate the factors or combinations thereof that govern liposome/water Lipophilicity, namely (a) hydrophobic interactions alone, (b) hydrophobic and polar interactions, and (c) conformational effects plus hydrophobic and ionic interactions. The next part presents two studies taken from the field of QSAR to exemplify the use of liposome/water Lipophilicity in structure-disposition and structure-activity relationships. In the conclusion, we summarize the interests and limitations of this technology and point to promising developments.
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Lipophilicity and solvation of anionic drugs.
Chemistry (Weinheim an der Bergstrasse Germany), 2002Co-Authors: Géraldine Bouchard, Bernard Testa, Pierre-alain Carrupt, Véronique Gobry, Hubert H. GiraultAbstract:This paper first gives a brief review of the main techniques used to measure the Lipophilicity of neutral and ionic drugs, namely the shake-flask method, potentiometry, and cyclic voltammetry at liquid-liquid interfaces. The Lipophilicity of 28 acidic compounds with various functional groups was studied by potentiometry and cyclic voltammetry in the n-octanol/water and 1,2-dichloroethane/water systems in order to complement our understanding of the Lipophilicity of neutral and ionized acids and to clarify the solvation mechanisms responsible for their partition. The parameter diff (log P(N-A)(dce)) (i.e., log P of the neutral acid minus standard log P of the conjugated anion in 1,2-dichloroethane/water) was shown to depend not only on intramolecular interactions and conformational effects in the neutral and anionic forms, but also on the delocalization of the negative charge in the anion, confirming the ability of Born's solvation model to describe qualitatively the effect of the molecular radius on the Lipophilicity of ions.
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The influence of Lipophilicity on the pharmacokinetic behavior of drugs: Concepts and examples
Perspectives in Drug Discovery and Design, 2000Co-Authors: Bernard Testa, Patrizia Crivori, Marianne Reist, Pierre-alain CarruptAbstract:In this review, we first examine the contextual background of structure–pharmacokinetic relationships. Some concepts in drug disposition are briefly recalled, and inherent difficulties instructure–pharmacokinetic relationships are outlined. Lipophilicity is then investigated in the light of the intermolecular and intramolecular interactions it encodes. In the main body of the review, a number of pharmacokinetic processes are examined for their relations with Lipophilicity. These processes are taken in a logical sequence of permeation, absorption (intestine, skin, cornea, brain), plasma protein binding, tissue distribution, volume of distribution and renal clearance. Relations between metabolism and Lipophilicity are more complex, since biotransformation involves both low-energy (enzyme binding) and high-energy (catalysis) processes. Only the former may be related to Lipophilicity. The conclusion argues against faulty statistics and over-interpretation.
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Lipophilicity in drug action and toxicology
1996Co-Authors: Vladimir Pliska, Bernard Testa, Han Van De WaterbeemdAbstract:Lipophilicity: the empirical tool and the fundamental objective - an introduction, V. Pliska, B. Testa and H. Van de Waterbemmd Lipophilicity: a history, M.S. Tute thermodynamics of van der Waals and hydrophobic interactions, R. Zahradnik and P. Hobza intramolecular interactions encoded in Lipophilicity: their nature and significance, B. Testa, P.-A. Carrupt, P. Gaillard and R.-S. Tsai Lipophilicity measurement by reversed-phase high-performance liquid chromatography (RP-HPLC), H. van de Waterbeemd, M. Kansy, B. Wagner and H. Fischer centrifugal partition chromatography for Lipophilicity measurements, R.-S. Tsai, G. Lisa, P.-A. Carrupt and B. Testa assessment of distribution-pH profiles, A. Avdeef estimation of Lipophilicity by reversed-phase thin-layer chromatography, R. Mannhold, K. Dross and C. Sonntag the future of log P calculation, A.J. Leo theoretical calculation of partition coefficients, W.G. Richards cellular automata model of partitioning between liquid phases, L.B. Kier and C.-K. Cheng the molecular Lipophilicity potential (MLP): a new tool for log P calculations and docking, and in comparative molecular field analysis (CoMFA), P.-A. Carrupt, et al hydrophobic fields in quantitative structure-activity relationships, G. Folkers and A. Merz physico-chemical and biological factors that influence a drug's cellular permeability by passive diffusion, R.A. Conradi, et al the role of Lipophilicity in biological response to drugs and endogenous ligands, V. Pliska membrane transport and cellular distribution, S. Balaz applications of a solvation equation to drug transport properties, M.H. Abraham and H.S. Chadra environmental hazard assessment using Lipophilicity data, R.L. Lipnick Lipophilicity in peptide chemistry and peptide drug design, J.-L. Fauchere side chain Lipophilicity of noncoded alpha-amino acids: pi-values the application of the intermolecular force model to bioactivity, peptide and protein quantitative structure-activity relationships, M. Charton Lipophilicity descriptors for structure-property correlation studies: overview of experimental and theoretical methods and a benchmark of log " calculations, H. van de Waterbeemd and R. Mannhold.
Gy. Kéri - One of the best experts on this subject based on the ideXlab platform.
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Lipophilicity and antiproliferative activity profiling of 2-benzylidencycloalkanones.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2007Co-Authors: Balazs Hallgas, Masahiko Idei, Gy. Kéri, Zsófia Dobos, Attila Agócs, Tamás Loránd, György MészárosAbstract:High performance liquid chromatographic (HPLC) method has been developed to separate the members of a library including 24 benzylidenecycloalkanone-type structures and to characterize their Lipophilicity. The experimental Lipophilicity data (k) of the compounds have been compared with their calculated Lipophilicity parameters (CLOGP). In general, good correlations between the measured and calculated lipophilicities have been found and these results were in good accordance with our previously data obtained in case of structurally related molecular libraries. In addition, cytotoxicity screening has been performed to determine the antiproliferative activity of these compounds. Some of the investigated compounds possessed noticeable inhibitory potential. Based on the correlation between the antiproliferative activity and experimentally determined Lipophilicity of the molecules investigated, limited structural demands to obtain more potent compounds can be exhibited to support the synthetic design.
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Comparison of measured and calculated Lipophilicity of substituted aurones and related compounds
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2004Co-Authors: Balazs Hallgas, Tamas Patonay, Attila Kiss-szikszai, Zs Dobos, Ferenc Hollósy, Dániel Erős, László Őrfi, Gy. Kéri, Masahiko IdeiAbstract:A molecule library containing 55 aurone- and thioaurone-type structures has been designed and synthesised. Reversed phase high performance liquid chromatographic (RP-HPLC) method has been developed to separate these compounds and to characterise their Lipophilicity by experimental method (k'). The experimental Lipophilicity data have been compared with the computer calculated Lipophilicity parameters (CLOGPs) of the same molecules. In general, good correlations between the measured and calculated lipophilicities have been found with the exception of structure isomers and compounds capable for hydrogen bonding. The chromatographic method was suitable to separate the structure (ortho and para) isomers of aurone and thioaurones and was sensitive enough to differentiate their lipophilicities. Our findings suggest the usefulness of the chromatographic method in fast characterisation of the Lipophilicity of structurally closely related molecules.
Philippe Millet - One of the best experts on this subject based on the ideXlab platform.
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Design of iodinated radioligands for SPECT imaging of central human 5-HT4R using a ligand Lipophilicity efficiency approach
Bioorganic Chemistry, 2020Co-Authors: Victor Babin, Benjamin Tournier, Audrey Davis, Emmanuelle Dubost, Gilbert Pigrée, Jean-françois Lohier, Vincent Reboul, Thomas Cailly, J.-p. Bouillon, Philippe MilletAbstract:A series of iodinated ligands for the SPECT imaging of 5-HT4 receptors was designed starting from the previously reported hit MR-26132. We focused on the modulation of the piperidine-containing lateral chain by introducing hydrophilic groups in order to decrease the liphophilicity of the new ligands. All the synthesized compounds were tested for their binding affinities on 5-HT4Rs and based on the Ligand Lipophilicity Efficiency approach, compound 13 was further selected for radioiodination with iodine-125 and imaging experiments. Compound 13 showed its ability to displace the specific signal of the reference compound [125I]SB-207710 but no significant detection of [125I]13 was observed in vivo in SPECT experiments.
