DC Field | Value | Language |
---|---|---|
dc.contributor.author | Milbank, JBJ | - |
dc.contributor.author | Stevenson, RJ | - |
dc.contributor.author | Ware, DC | - |
dc.contributor.author | Chang, JYC | - |
dc.contributor.author | Tercel, M | - |
dc.contributor.author | Ahn, GO | - |
dc.contributor.author | Wilson, WR | - |
dc.contributor.author | Denny, WA | - |
dc.date.accessioned | 2016-03-31T09:14:55Z | - |
dc.date.available | 2016-03-31T09:14:55Z | - |
dc.date.created | 2012-02-08 | - |
dc.date.issued | 2009-11-12 | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.other | 2009-OAK-0000024677 | - |
dc.identifier.uri | https://oasis.postech.ac.kr/handle/2014.oak/16887 | - |
dc.description.abstract | A series of metal complexes were prepared as potential prodrugs of the extremely toxic DNA minor groove alkylator 1-(chloromethyl)-5-hydroxy-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline (seco-6-azaCBI-TMI) and close analogues. The pyrrolo[3,2-f]quinoline cytotoxins were prepared from 2-methoxy-4-nitroaniline in a nine-step synthesis involving a Skraup construction of a quinoline intermediate, its appropriate functionalization, and a final radical cyclization. The metal complexes were prepared from these and the labile metal complex synthons [Co-(cyclen)(OTf)(2)](+), [Cr(acac)(2)(H2O)(2)](+,) and [Co-2(Me(2)dtc)(5)](+). The cobalt complexes were considerably more stable than the free effectors and showed significant attenuation of the cytotoxicity of the latter, with IC50 ratios (complex/effector) of 50- to 150-fold, and substantial hypoxic cell selectivity, with IC50 ratios (oxic/hypoxic cells) of 20- to 40-fold. The cobalt complexes were also efficiently activated by ionizing radiation, with G values for loss of the compound close to the theoretical value for one-electron reduction of 0.68 mu mol/J. This work extends earlier observations that cobalt cyclen complexes are suitable for both the bioreductive and radiolytic release of potent pyrrolo[3,2-f]quinoline effectors. | - |
dc.description.statementofresponsibility | X | - |
dc.language | English | - |
dc.publisher | American Chemical Society | - |
dc.relation.isPartOf | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.subject | RADIATION-ACTIVATED PRODRUGS | - |
dc.subject | GROOVE ALKYLATING-AGENTS | - |
dc.subject | EXPLOITING TUMOR HYPOXIA | - |
dc.subject | N-O BONDS | - |
dc.subject | COBALT(III) COMPLEXES | - |
dc.subject | REDUCTIVE CLEAVAGE | - |
dc.subject | ANTICANCER DRUGS | - |
dc.subject | CBI-TMI | - |
dc.subject | DUOCARMYCINS | - |
dc.subject | MUSTARDS | - |
dc.title | Synthesis and Evaluation of Stable Bidentate Transition Metal Complexes of 1-(Chloromethyl)-5-hydroxy-3-(5,6,7-trimethoxyindol-2-ylcarbonyl)-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline (seco-6-azaCBI-TMI) as Hypoxia Selective Cytotoxins | - |
dc.type | Article | - |
dc.contributor.college | 융합생명공학부 | - |
dc.identifier.doi | 10.1021/JM9008746 | - |
dc.author.google | Milbank, JBJ | - |
dc.author.google | Stevenson, RJ | - |
dc.author.google | Ware, DC | - |
dc.author.google | Chang, JYC | - |
dc.author.google | Tercel, M | - |
dc.author.google | Ahn, GO | - |
dc.author.google | Wilson, WR | - |
dc.author.google | Denny, WA | - |
dc.relation.volume | 52 | - |
dc.relation.issue | 21 | - |
dc.relation.startpage | 6822 | - |
dc.relation.lastpage | 6834 | - |
dc.contributor.id | 10967338 | - |
dc.relation.journal | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.relation.index | SCI급, SCOPUS 등재논문 | - |
dc.relation.sci | SCI | - |
dc.collections.name | Journal Papers | - |
dc.type.rims | ART | - |
dc.identifier.bibliographicCitation | JOURNAL OF MEDICINAL CHEMISTRY, v.52, no.21, pp.6822 - 6834 | - |
dc.identifier.wosid | 000271427900034 | - |
dc.date.tcdate | 2019-01-01 | - |
dc.citation.endPage | 6834 | - |
dc.citation.number | 21 | - |
dc.citation.startPage | 6822 | - |
dc.citation.title | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.citation.volume | 52 | - |
dc.contributor.affiliatedAuthor | Ahn, GO | - |
dc.identifier.scopusid | 2-s2.0-71049165150 | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.wostc | 35 | - |
dc.description.scptc | 36 | * |
dc.date.scptcdate | 2018-05-121 | * |
dc.type.docType | Article | - |
dc.subject.keywordPlus | EXPLOITING TUMOR HYPOXIA | - |
dc.subject.keywordPlus | N-O BONDS | - |
dc.subject.keywordPlus | COBALT(III) COMPLEXES | - |
dc.subject.keywordPlus | REDUCTIVE CLEAVAGE | - |
dc.subject.keywordPlus | CBI-TMI | - |
dc.subject.keywordPlus | DUOCARMYCINS | - |
dc.subject.keywordPlus | MUSTARDS | - |
dc.subject.keywordPlus | PRODRUGS | - |
dc.subject.keywordPlus | CC-1065 | - |
dc.subject.keywordPlus | ANALOGS | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
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