1,720,986 research outputs found
Highly selective compounds for the antibody-directed enzyme prodrug therapy of cancer
No full textAntibody-directed enzyme prodrug therapy ( ADEPT) is a recent development for a selective treatment of cancer, based on site-directed formation at the surface of malignant cells of cytotoxic compounds from non-toxic prodrugs with a conjugate of an appropriate enzyme and a monoclonal antibody which binds to tumour-associated antigens. New potent prodrugs of analogues of the antibiotic CC-1065 have been developed. These show a remarkable selectivity with a Q( IC50) value of up to more than 3000. Moreover, the formed drug has a high potency with an IC50 of 30 pM
Enzyme and proton-activated prodrugs for a selective cancer therapy
No full textThis review is a survey of two approaches for a selective anticancer therapy that are based on a specific cleavage of specially designed non-toxic prodrugs with the liberation of a cytotoxic compound either by antibody-enzyme conjugates targeted to tumor-associated antigens or by acid-catalyzed hydrolysis of the prodrugs due to the increased concentration of hydronium ions in malignant tissue under hyperglycemic conditions. Herein, the design, synthesis and the biological testing of prodrugs are described
A concise and efficient synthesis of seco-duocarmycin SA
No full textA short and efficient synthesis of seco-duocarmycin SA (3), a highly potent cytostatic agent and direct precursor of the natural product duocarmycin SA (1), has been achieved. Starting from commercially available 2-methoxy-4-nitroaniline (4) the synthetic protocol contains a Fischer indole synthesis to introduce the heterocyclic scaffold and a radical 5-exo-trig cyclization to furnish the (chloromethyl)indoline ring system as key reactions. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
A concise and efficient synthesis of seco-duocarmycin SA
No full textA short and efficient synthesis of seco-duocarmycin SA (3), a highly potent cytostatic agent and direct precursor of the natural product duocarmycin SA (1), has been achieved. Starting from commercially available 2-methoxy-4-nitroaniline (4) the synthetic protocol contains a Fischer indole synthesis to introduce the heterocyclic scaffold and a radical 5-exo-trig cyclization to furnish the (chloromethyl)indoline ring system as key reactions. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis and biological evaluation of novel analogues and prodrugs of the cytotoxic antibiotic CC-1065 for selective cancer therapy
No full textThis paper describes novel seco-analogues 25-27 of the cytotoxic antibiotic CC-1065 (1) and their prodrugs 5, 6a, and 6b, for antibody-directed enzyme prodrug therapy (ADEPT), The partially hydrogenated seco-CCI-analogue 7 and the corresponding methyl-CCI analogues 8a and 8b were synthesized by alkylation of 9 with 15 and 16, respectively, followed by radical cyclization and deprotection. Treatment of 7, 8a, and 8b with the galactose trichloroacetimidate 21 and the bisindolyl-carboxylic acid 20 in the presence of EDC followed by solvolysis gave the desired prodrugs 5, 6a, and 6b, respectively, Compounds 25-27 were prepared by treatment of 7, 8a, and 8b with 20 after deprotection, In vitro tests showed a strong cytotoxicity for 25 and a fairly low toxicities for 26 and 27. However, the selectivity of the prodrugs 5, 6a, and 6b was not sufficient for ADEPT, Interestingly, 8a and 8b did not undergo Winstein cyclization to produce the spirocyclopropylcyclohexadienone moiety. (C) Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
Synthesis and biological evaluation of novel analogues and prodrugs of the cytotoxic antibiotic CC-1065 for selective cancer therapy
No full textThis paper describes novel seco-analogues 25-27 of the cytotoxic antibiotic CC-1065 (1) and their prodrugs 5, 6a, and 6b, for antibody-directed enzyme prodrug therapy (ADEPT), The partially hydrogenated seco-CCI-analogue 7 and the corresponding methyl-CCI analogues 8a and 8b were synthesized by alkylation of 9 with 15 and 16, respectively, followed by radical cyclization and deprotection. Treatment of 7, 8a, and 8b with the galactose trichloroacetimidate 21 and the bisindolyl-carboxylic acid 20 in the presence of EDC followed by solvolysis gave the desired prodrugs 5, 6a, and 6b, respectively, Compounds 25-27 were prepared by treatment of 7, 8a, and 8b with 20 after deprotection, In vitro tests showed a strong cytotoxicity for 25 and a fairly low toxicities for 26 and 27. However, the selectivity of the prodrugs 5, 6a, and 6b was not sufficient for ADEPT, Interestingly, 8a and 8b did not undergo Winstein cyclization to produce the spirocyclopropylcyclohexadienone moiety. (C) Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
‐Analogs of the Antitumor Antibiotic CC‐1065 by Two Consecutive Transition Metal‐Initiated Transformations
No full textNovel seco-analogs of CC-1065 1 were synthesized from comercially available nitroaniline by reduction, bromination, bisulfonation and bisallylation followed by reaction with tert-butyllithium, zirconocene and iodine. The obtained quinoline 6 was then transformed into 17 and 18, which, upon treatment with Pd-0, led to 21 and 22, respectively. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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