Herzig, Alf

[["dc.bibliographiccitation.firstpage","1634"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","European Journal of Organic Chemistry"],["dc.bibliographiccitation.lastpage","1645"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Herzig, T."],["dc.contributor.author","Feuerstein, T."],["dc.contributor.author","Schuberth, I."],["dc.date.accessioned","2018-11-07T10:30:10Z"],["dc.date.available","2018-11-07T10:30:10Z"],["dc.date.issued","2002"],["dc.description.abstract","This 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."],["dc.identifier.isi","000175636300006"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43808"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","1434-193X"],["dc.title","Synthesis and biological evaluation of novel analogues and prodrugs of the cytotoxic antibiotic CC-1065 for selective cancer therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","758"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","ChemBioChem"],["dc.bibliographiccitation.lastpage","765"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Herzig, T."],["dc.contributor.author","Fecher, A."],["dc.contributor.author","Haunert, F."],["dc.contributor.author","Schuberth, I."],["dc.date.accessioned","2018-11-07T08:33:50Z"],["dc.date.available","2018-11-07T08:33:50Z"],["dc.date.issued","2001"],["dc.description.abstract","Novel prodrugs of the cytotoxic antibiotic CC-1065 for an antibody directed enzyme prodrug therapy (ADEPT) were prepared that show an excellent selectivity with a high toxicity of the corresponding drug. In particular,a the seco-CBI analogue of CC-1065, 1-chloromethyl-5-hydroxy-1,2-dihydro-3H-benz[e]indole as well as the novel methyl-seco-CBI analogue 1-(1'-chloroethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole, were synthesized and transformed into their galactosides 10a and 10b, respectively. These galactosides can be cleaved with beta -D-galactosidase to give the free cytoxic compounds. They were tested in in vitro cytotoxicity assays by using human bronchial carcinoma cells of line A549 in the presence and in the absence of beta -D-galactosidase. While the seco-CBI prodrugs revealed only modest selectivity, prodrugs of the methyl-seco-CBI analogue bearing an anti orientation of the substituents at the two stereogenic centers of the N-heterocycle displayed an excellent selectivity with an ED50 quotient of about 750. The cytotoxicity of the corresponding phenol was rather high, with an ED50 of 1.3 nM. The diastereomer with a syn orientation at the stereogenic centers was much less toxic."],["dc.identifier.doi","10.1002/1439-7633(20011001)2:10<758::AID-CBIC758>3.0.CO;2-G"],["dc.identifier.isi","000171410000006"],["dc.identifier.pmid","11948858"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17684"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","1439-4227"],["dc.title","Highly selective glycosylated prodrugs of cytostatic CC-1065 analogues for antibody-directed enzyme tumor therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1929"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Bioorganic & Medicinal Chemistry"],["dc.bibliographiccitation.lastpage","1939"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Lieb, M."],["dc.contributor.author","Herzig, T."],["dc.contributor.author","Haunert, F."],["dc.contributor.author","Schuberth, I."],["dc.date.accessioned","2018-11-07T08:53:54Z"],["dc.date.available","2018-11-07T08:53:54Z"],["dc.date.issued","2001"],["dc.description.abstract","Immuno-conjugates obtained by linking enzymes with appropriate monoclonal antibodies, which bind to tumor-associated antigens, can be employed in a tumor-selective antibody directed enzyme prodrug therapy (ADEPT). For this strategy the glycosides 17a-c were prepared as prodrugs of CI-TMI 14 which is a structurally simplified analogue of the highly potent antitumor agent duocarmycin SA 2. Exposure of 17a-c to cultured carcinoma cells of line A549 displayed a very low toxicity; however, after addition of the corresponding enzymes and exposure for 24 h at prodrug concentrations of <0.1 M the proliferation of the carcinoma cells was inhibited almost completely with ED50prodrug/ED50drug of UP to 270 in the presence and in the absence of the enzyme. The synthesis of 17a-c was achieved by transformation of nitroanisidine 6 into 12 which was glycosidated to give 16a-c. Removal of the silyl groups, introduction of a chlorine atom and solvolysis of the acetal groups led to 17a-c, of which 17a and 17c are promising candidates for further elaboration. (C) 2001 Elsevier Science Ltd. All rights reserved."],["dc.identifier.doi","10.1016/S0968-0896(01)00098-0"],["dc.identifier.isi","000169580500033"],["dc.identifier.pmid","11425596"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22537"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","0968-0896"],["dc.title","A strategy for tumor-selective chemotherapy by enzymatic liberation of seco-duocarmycin SA-derivatives from nontoxic prodrugs"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]