Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Type of Medium
Language
Year
  • 1
    Language: English
    In: Journal of medicinal chemistry, 09 June 2016, Vol.59(11), pp.5449-61
    Description: Chemotherapeutic treatment of cancer often fails due to overexpression of the ATP-binding cassette (ABC) transport proteins, like ABCG2, triggering active efflux of various structurally unrelated drugs. This so-called multidrug resistance (MDR) may be reversed by selective, potent, and nontoxic inhibitors of ABCG2. As only a few potent inhibitors are known, new compounds based on a 4-substituted-2-phenylquinazoline scaffold were investigated. Substitution with hydroxy, cyano, nitro, acetamido, and fluoro led to high inhibitory activities toward ABCG2. The ability to reverse MDR of the most active compounds was confirmed in a MTT efficacy assay. Moreover, a negligibly low intrinsic cytotoxicity was found resulting in a high therapeutic ratio. Investigations of the inhibitory activity toward ABCB1 and ABCC1 yielded a high selectivity toward ABCG2 for the quinazoline compounds. Quinoline-based analogues showed lower inhibitory activity and selectivity. The study yielded a variety of promising compounds, some with superior properties compared to those of the standard inhibitor Ko143.
    Keywords: ATP Binding Cassette Transporter, Subfamily G, Member 2 -- Antagonists & Inhibitors ; Neoplasm Proteins -- Antagonists & Inhibitors ; Quinazolines -- Pharmacology ; Quinolines -- Pharmacology
    ISSN: 00222623
    E-ISSN: 1520-4804
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Journal of medicinal chemistry, 25 May 2017, Vol.60(10), pp.4474-4495
    Description: Multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transport proteins remains a major problem in the chemotherapeutic treatment of cancer and might be overcome by inhibition of the transporter. Because of the lack of understanding, the complex mechanisms involved in the transport process, in particular for breast cancer resistance protein (BCRP/ABCG2), there is a persistent need for studies of inhibitors of ABCG2. In this study, we investigated a systematic series of 4-substituted-2-pyridylquinazolines in terms of their inhibitory potency as well as selectivity toward ABCG2. For comparison, the quinazoline scaffold was reduced to the significantly smaller 4-methylpyrimidine basic structure. Furthermore, the cytotoxicity and the ability to reverse MDR was tested with the chemotherapeutic agents SN-38 and mitoxantrone (MX). Interaction of the compounds with ABCG2 was investigated by a colorimetric ATPase assay. Enzyme kinetic studies were carried out with Hoechst 33342 as fluorescent dye and substrate of ABCG2 to elucidate the compounds binding modes.
    Keywords: ATP Binding Cassette Transporter, Subfamily G, Member 2 -- Antagonists & Inhibitors ; Pyrimidines -- Chemistry ; Quinazolines -- Chemistry
    ISSN: 00222623
    E-ISSN: 1520-4804
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Journal of medicinal chemistry, 26 April 2018, Vol.61(8), pp.3389-3408
    Description: Multidrug resistance (MDR) occurring during cancer chemotherapy is a major obstacle for effectiveness and response to therapy and is often caused by ATP-binding cassette (ABC) efflux transporters. Belonging to the family of ABC transporters, breast cancer resistance protein is getting more and more in the spotlight of research. As a strategy to overcome MDR, inhibitors of ABC transporters were synthesized, which could be applied in combination with cytostatic drugs. For this purpose, 2,4-disubstituted pyridopyrimidine derivatives were synthesized. The investigations confirmed three key characteristics of good inhibitors: a low intrinsic cytotoxicity and a high potency and selectivity toward ABCG2. For selected compounds the interaction with ABCG2 was elucidated and their effect on ATPase activity and conformation sensitive 5D3 antibody binding was investigated. Their ability to reverse MDR in coadministration with the active metabolite of irinotecan and mitoxantron was confirmed.
    Keywords: ATP Binding Cassette Transporter, Subfamily G, Member 2 -- Antagonists & Inhibitors ; Antineoplastic Agents -- Pharmacology ; Neoplasm Proteins -- Antagonists & Inhibitors ; Pyridines -- Pharmacology ; Pyrimidines -- Pharmacology
    ISSN: 00222623
    E-ISSN: 1520-4804
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Journal of medicinal chemistry, 13 September 2018, Vol.61(17), pp.7952-7976
    Description: Several members of the ABC transporter superfamily play a decisive role in the development of multidrug resistance (MDR) in cancer. One of these MDR associated efflux transporters is ABCG2. One way to overcome this MDR is the coadministration of potent inhibitors of ABCG2. In this study, we identified novel inhibitors containing a 2,4,6-substituted quinazoline scaffold. Introduction of a 6-nitro function led to extraordinarily potent compounds that were highly selective for ABCG2 and also able to reverse the MDR toward the chemotherapeutic drugs SN-38 and mitoxantrone. The binding of substrate Hoechst 33342 and the two potent inhibitors 31 and 41 which differ in their mechanism of inhibition was rationalized using the recently published cryo-EM structures of ABCG2. For a better understanding of the interaction between the inhibitors and ABCG2, additional investigations regarding the ATPase activity, the interaction with Hoechst 33342, and with the conformational sensitive 5D3 antibody were carried out.
    Keywords: ATP Binding Cassette Transporter, Subfamily G, Member 2 -- Antagonists & Inhibitors ; Antineoplastic Agents -- Chemistry ; Drug Resistance, Multiple -- Drug Effects ; Drug Resistance, Neoplasm -- Drug Effects ; Neoplasm Proteins -- Antagonists & Inhibitors ; Neoplasms -- Drug Therapy ; Quinazolines -- Chemistry
    ISSN: 00222623
    E-ISSN: 1520-4804
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: European Journal of Medicinal Chemistry, 20 October 2017, Vol.139, pp.587-611
    Description: Expression of ABCG2, a member of the ABC transporter superfamily, has been correlated to the clinical outcome of multiple cancers and is often associated with the occurrence of multidrug resistance (MDR) in chemotherapy. Inhibition of the transport protein by potent and selective inhibitors might be a way to treat cancer more efficiently and improve the therapy of cancer patients. Recently we reported the synthesis of new inhibitors based on a quinazoline scaffold. In the present study more structural variations were explored. Compounds with 3,4-dimethoxy groups and or nitro substituents were found to be highly potent inhibitors of ABCG2. The most potent compound was more than five-fold more potent than Ko143, one of the best inhibitors of ABCG2. To determine the new compounds selectivity toward ABCG2 their inhibitory effects on ABCB1 and ABCC1 were also investigated identifying selective as well as broadspectrum inhibitors. Furthermore, intrinsic cytotoxicity and efficacy regarding the reversal of multidrug resistance toward SN-38 and mitoxantrone were explored. The most potent compounds were able to reverse the resistance toward the cytostatic agents with EC values below 20 nM. Additionally, the type of interaction between inhibitors and the ABCG2 substrate Hoechst 33342 was investigated yielding competitive and non-competitive interactions suggesting different modes of binding. Finally the effect of the derivatives on vanadate-sensitive ATPase activity of ABCG2 was determined. According to the different effects on ATPase activity we conclude the existence of different binding sites. This study provides the structural requirements for high potency inhibition and elucidates the interaction with ABCG2 setting the basis for further studies.
    Keywords: ABC Transporter ; Inhibitor ; Abcg2 ; Quinazolines ; Bcrp ; Pharmacy, Therapeutics, & Pharmacology ; Chemistry
    ISSN: 0223-5234
    E-ISSN: 1768-3254
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: European Journal of Medicinal Chemistry, 01 January 2019, Vol.161, pp.506-525
    Description: Multidrug resistance (MDR) is a major obstacle for effective chemotherapeutic treatment of cancer frequently leading to failure of the therapy. MDR is often associated with the overexpression of ABC transport proteins like ABCB1 or ABCG2 which efflux harmful substances out of cells at the cost of ATP hydrolysis. One way to overcome MDR is to apply potent inhibitors of ABC transporters to restore the sensitivity of the cells toward cytostatic agents. This study focusses on the synthesis and evaluation of novel 2,4-disubstituted quinazoline derivatives regarding the structure-activity-relationship (SAR), their ability to reverse MDR and their mode of interaction with ABCG2. Hence, the inhibitory potency and selectivity toward ABCG2 was determined. Moreover, the intrinsic cytotoxicity and the reversal of MDR were investigated. Interaction type studies with the substrate Hoechst 33342 and conformational analyses of ABCG2 with 5D3 monoclonal antibody were performed for a better understanding of the underlying mechanisms. In our study we could further enhance the inhibitory effect against ABCG2 (compound , IC : 55 nM) and identify the structural features that are crucial for inhibitory potency, the impact on transport activity and binding to the protein.
    Keywords: ABC Transporter ; Inhibitor ; Abcg2 ; Quinazolines ; SAR ; Pharmacy, Therapeutics, & Pharmacology ; Chemistry
    ISSN: 0223-5234
    E-ISSN: 1768-3254
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Physical review. E, Statistical, nonlinear, and soft matter physics, April 2012, Vol.85(4 Pt 1), pp.041924
    Description: We describe a method for the analysis of the distribution of displacements, i.e., the propagators, of single-particle tracking measurements for the case of obstructed subdiffusion in two-dimensional membranes. The propagator for the percolation cluster is compared with a two-component mobility model against Monte Carlo simulations. To account for diffusion in the presence of obstacle concentrations below the percolation threshold, a propagator that includes the transient motion in finite percolation clusters and hopping between obstacle-induced compartments is derived. Finally, these models are shown to be effective in the analysis of Kv2.1 channel diffusive measurements in the membrane of living mammalian cells.
    Keywords: Molecular Imaging -- Instrumentation ; Nanoparticles -- Ultrastructure ; Refractometry -- Instrumentation
    ISSN: 24700045
    E-ISSN: 1550-2376
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Nature, 26 May 2016, Vol.533(7604), pp.527-31
    Description: About half of present-day cloud condensation nuclei originate from atmospheric nucleation, frequently appearing as a burst of new particles near midday. Atmospheric observations show that the growth rate of new particles often accelerates when the diameter of the particles is between one and ten nanometres. In this critical size range, new particles are most likely to be lost by coagulation with pre-existing particles, thereby failing to form new cloud condensation nuclei that are typically 50 to 100 nanometres across. Sulfuric acid vapour is often involved in nucleation but is too scarce to explain most subsequent growth, leaving organic vapours as the most plausible alternative, at least in the planetary boundary layer. Although recent studies predict that low-volatility organic vapours contribute during initial growth, direct evidence has been lacking. The accelerating growth may result from increased photolytic production of condensable organic species in the afternoon, and the presence of a possible Kelvin (curvature) effect, which inhibits organic vapour condensation on the smallest particles (the nano-Köhler theory), has so far remained ambiguous. Here we present experiments performed in a large chamber under atmospheric conditions that investigate the role of organic vapours in the initial growth of nucleated organic particles in the absence of inorganic acids and bases such as sulfuric acid or ammonia and amines, respectively. Using data from the same set of experiments, it has been shown that organic vapours alone can drive nucleation. We focus on the growth of nucleated particles and find that the organic vapours that drive initial growth have extremely low volatilities (saturation concentration less than 10(-4.5) micrograms per cubic metre). As the particles increase in size and the Kelvin barrier falls, subsequent growth is primarily due to more abundant organic vapours of slightly higher volatility (saturation concentrations of 10(-4.5) to 10(-0.5) micrograms per cubic metre). We present a particle growth model that quantitatively reproduces our measurements. Furthermore, we implement a parameterization of the first steps of growth in a global aerosol model and find that concentrations of atmospheric cloud concentration nuclei can change substantially in response, that is, by up to 50 per cent in comparison with previously assumed growth rate parameterizations.
    Keywords: Sciences (General) ; Physics;
    ISSN: 00280836
    E-ISSN: 1476-4687
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: Journal of Neurology, 7/2004, Vol.251(7)
    Description: Byline: Wilhelm Kuker (1), Michael Weller (2), Uwe Klose (1), Hilmar Krapf (1), Johannes Dichgans (2), Thomas Nagele (1) Keywords: spinal infarction; DWI; MRI; spinal cord Abstract: Abstract. Infarction is a rare cause of spinal cord dysfunction. Whereas diffusion-weighted (DW) MRI has been established as a highly sensitive technique for assessing acute cerebral ischemia, its role in spinal cord infarction remains to be determined. The purpose of this study is to present the signal characteristics of acute spinal cord ischemia using DWMRI within the first two days and after one week. MRI including DW imaging (DWI) was performed in three patients with acute spinal cord dysfunction 8, 12 and 30 hours after the onset of symptoms and repeated after one week in two patients. Two initial scans included EPI DW sequences in transverse and sagittal orientation. The remaining examinations were performed with an optimised highspatial resolution DWI sequence in the transverse plane. The diagnosis of spinal cord ischemia was established by imaging, clinical history and CSF analysis. T2 signal abnormality and restricted diffusion was demonstrated in all initial examinations. Transverse DW sequences had the highest sensitivity. The spinal infarctions were mainly located in the centre of the spinal cord and the grey matter. Contrast enhancement was absent. After one week, the restricted diffusion had normalised (pseudo normalisation) whereas the T2 signal changes had become more prominent. Restricted diffusion in the course of spinal cord ischemic infarction can be demonstrated using DW-MRI. Whereas a diffusion abnormality can be found after few hours, it does not last for longer than one week. At this time, the establishment of the diagnosis has to rely mainly on T2-weighted images with additional post contrast T1-weighted images being useful. Author Affiliation: (1) Department of Neuroradiology, University Hospital Tubingen, Hoppe-Seyler-Str. 3, 72076, Tubingen, Germany (2) Department of Neurology, University of Tubingen Medical School, Tubingen, Germany Article History: Registration Date: 01/01/2004 Received Date: 12/09/2003 Accepted Date: 09/02/2004
    Keywords: Magnetic Resonance Imaging -- Usage ; Spinal Cord Diseases -- Causes Of ; Brain Infarction -- Complications And Side Effects;
    ISSN: 0340-5354
    E-ISSN: 1432-1459
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    In: Bijdragen tot de Taal-, Land- en Volkenkunde 128(1), 143-208 (1972)
    Description: - J. Huizinga, Ashley Montagu, Man: His first two million years. Columbia Univ. Press, New York and London, 1969, 262 pag. - W. van Hoorn, Warner Muensterberger, Man and his culture: Psychoanalytic anthropology after ‘Totem and Taboo’. Rapp and Whiting, London 1969. 397 p. - J.W.I.M. Simons, W.M. Pfeiffer, Transkulturelle Psychiatrie. George Thieme Verlag, Stuttgart 1971. 166 S., 9 Abb., 22 Tab. - J.W.I.M. Simons, J.H. Orley, Culture and mental illness. East African Publishing House, Nairobi 1970. 82 p. - E.M. Uhlenbeck, P.E. de Josselin de Jong, Contact der Continenten, Bijdrage tot het begrijpen van niet-westerse samenlevingen. Universitaire Pers Leiden, 1969, 144 pp. - H.J.M. Claessen, A.J.F. Köbben, Van primitieven tot medeburgers, 2e druk. Van Gorcum, Assen 1971. 278 blz. - R.J. Mohr, Antropica. Gedenkschrift zum 100. Geburtstag von P. Wilhelm Schmidt. Gesammelte Aufsätze, herausgegeben vom Anthropos-Institut. Studia Instituti Anthropos Vol. 21. Verlag des Anthropos-Instituts St. Augustin bei Bonn 1968. XII + 452 S. - Jairus Banaji, E. Nelson Hayes, Claude Lévi-Strauss: the anthropologist as hero. MIT Press, Cambridge, Mass. 1970. 264 pp., Tanya Hayes (eds.) - J. Prins, Banton Michael, Political systems and the distribution of power, A.S.A. Monographs 2, London: Tavistock Publications; New York: Fred. A. Praeger, Publishers, 1965. XLIII en 142 bladzijden. - Ellen N. Buschkens-Holle, H.J.M. Duller, ‘Ekonomische ontwikkeling en ondernemerschap - een ekonomisch-sociologische benadering van het ontwikkelingsverschijnsel. - H. A. Luning, Sandra Wallman, Take out hunger. Two case studies of rural development in Basutoland. University of London, The Athlone Press, London 1969. 178 + xii pp. - A. A. Trouwborst, Vinigi L. Grottanelli, Het Leven der Volken: Culturele Antropologie. Deel 4, Akkerbouwers, Veehouders. Sesam, Bosch & Keuning N.V., Baarn 1969/70. 248 blz., ills. - I. Gurvic’, A.P. Okladnikov, Yakutia. H.N. Michael, ed. McGill-Queen’s University Press, Montreal & London 1970. 499 p., 84 ills., 4 maps. - Arne Biörnstad, Odd Nordland, Brewing and beer traditions in Norway. Universitetsforlaget, Oslo-Bergen-Tromsö 1969. 320 p., 114 ills. - A.H.J. Prins, R. G. P. Hill, The Lapps to-day in Finland, Norway and Sweden, vol. II; Oslo (Universitetsforlag) 1969, 357 pag., K. Nickul (eds.) - C. Baks, Dorothy Willner, Nation-building and community in Israel. Princeton University Press, Princeton, New Jersey, 1969. 478 pp. - Rudolf van Zantwijk, Hugo G. Nutini, San Bernardino Contla, Marriage and Family structure in a Tlaxcalan Municipio. University of Pittsburgh Press, Pittsburgh 1968. VIII + 420 blz. - Rudolf van Zantwijk, Shuichi Nagata, Modern transformations of Moenkopi Pueblo. Illinois Studies in Anthropology, nr. 6. University of Illinois Press, Urbana, Chicago, London 1970. XVII + 336 blz., 25 ills. - Th. J. C. Brasser, Robin Fox, The Keresan Bridge; a problem in Pueblo ethnology. London School of Economics Monographs on Social Anthropology, No. 35. The Athlone Press, London, 1967. xii & 216 pp. - A. N. J. den Hollander, Ulf Hannerz, Soulside; Inquiries into ghetto culture and community. New York & London, Columbia University Press, 1969, 236 blz. - H.J.M. Claessen, J.W. Schulte Nordholt, In de schaduw van een groot licht. De negerrevolutie in Amerika. Het zuiden 1954-1966. Van Loghum en Slaterus, Deventer 1971. 332 pp., ill., literatuuropgave, register. - Stephen Wild, Hugh Tracey, Chopi musicians. Oxford University Press for International African Institute. London, 1970. 193 pp., 15 plates, 7 diagrams, 2 maps. - A.A. Trouwborst, Meyer Fortes, Time and social structure and other essays. London school of economics monographs on social anthropology no. 40. University of London: The Athlone Press, New York: Humanities Press Inc. 1970, IX, 287 p., illustr. - A. Maesen, Michael Swithenbank, Ashanti Fetish Houses. Ghana Universities Press, Oxford University Press, Accra 1969. 68 pp., 69 fig., I K., bibl. - C. Oppong, Eva Krapf-Askari, Yoruba towns and cities. An enquiry into the nature of urban social phenomenon. Clarendon Press, Oxford University Press, Oxford 1969. 192 p., maps, plans, diagrams. - M.W. Aig-Ojehomon-Ketting, G.K. Nukunya, Kinship and marriage among the Anlo Ewe. London school of economics monographs on social anthropology no. 37. London 1969, 217 + LX pp. - A.A. Trouwborst, Valdo Pons, Stanleyville. An African urban community under Belgian administration. Published for the International African Institute by the Oxford University Press, London 1969. Pp. XXIV, 356, plates, maps, diagrams and tables. - J.L. Swellengrebel, T. Goudriaan, Stuti and Stava (Verhandelingen der Kon. Nederl. Akademie van Wetenschappen, Afd. Letterkunde, Nieuwe Reeks, Dl. 76). North-Holland Publishing Company - Amsterdam, London - 1971. 609 pp. 8 plates., C. Hooykaas (eds.)
    Source: Utrecht University
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages