DC Field | Value | Language |
---|---|---|
dc.contributor.author | Ahn, GO | - |
dc.contributor.author | Botting, KJ | - |
dc.contributor.author | Patterson, AV | - |
dc.contributor.author | Ware, DC | - |
dc.contributor.author | Tercel, M | - |
dc.contributor.author | Wilson, WR | - |
dc.date.accessioned | 2016-03-31T09:14:45Z | - |
dc.date.available | 2016-03-31T09:14:45Z | - |
dc.date.created | 2012-02-08 | - |
dc.date.issued | 2006-06-14 | - |
dc.identifier.issn | 0006-2952 | - |
dc.identifier.other | 2006-OAK-0000024683 | - |
dc.identifier.uri | https://oasis.postech.ac.kr/handle/2014.oak/16882 | - |
dc.description.abstract | Metabolic reduction can be used to activate prodrugs in hypoxic regions of tumours, but reduction by ionising radiation is also theoretically attractive. Previously, we showed that a cobalt(III) complex containing 8-hydroxyquinoline (8-HQ) and cyclen ligands releases 8-HQ efficiently on irradiation in hypoxic solutions [Ahn G-O, Ware DC, Denny WA, Wilson WR. optimization of the auxiliary ligand shell of cobalt(III)(8-hydroxyquinoline) complexes as model hypoxia-selective radiation-activated prodrugs. Radiat Res 2004;162:315-25]. Here we investigate an analogous Co(III) complex containing the potent DNA minor groove alkylator azachloromethylbenzindoline (azaCBI, (1) under bar) to determine whether it releases (1) under bar on radiolytic and/or enzymatic reduction under hypoxia. Monitoring by HPLC, the azaCBI ligand in the Co(III)(cyclen)(azaCBI) complex M slowly hydrolysed in aqueous solution, in contrast to the free ligand 1 which readily converted to its reactive cyclopropyl form. Irradiation of 2 (3050 mu M) in hypoxic solutions released (1) under bar with yields of 0.57 mu mol/J in formate buffer and 0.13 mu mol/J in human plasma. Using bioassay methods, cytotoxic activation by irradiation of at 1 mu M in hypoxic plasma was readily detectable at clinically relevant doses (>= 1 Gy), with a estimated yield of (1) under bar of 0.075 mu mol/J. Release of 1 from 2 was also observed in hypoxic HT29 cultures without radiation, with subsequent conversion of 1 to its O-glucuronide. Surprisingly, overexpression of human cytochrome P450 reductase in A549 cells did not increase the rate of metabolic reduction of 2, suggesting that other reductases and/or non-enzymatic reductants are responsible. Thus the cobalt(III) complex 2 is a promising prodrug capable of being activated to release a very potent cytotoxin when reduced by either ionising radiation or cells under hypoxic conditions. (c) 2006 Elsevier Inc. All rights reserved. | - |
dc.description.statementofresponsibility | X | - |
dc.language | English | - |
dc.publisher | Elsevier | - |
dc.relation.isPartOf | BIOCHEMICAL PHARMACOLOGY | - |
dc.subject | tumour hypoxia | - |
dc.subject | prodrug | - |
dc.subject | ionising radiation | - |
dc.subject | Co(III) complex | - |
dc.subject | CBI | - |
dc.subject | DNA minor groove alkylator | - |
dc.subject | MULTICELLULAR LAYER CULTURES | - |
dc.subject | PREDICTS RADIATION RESPONSE | - |
dc.subject | EXPLOITING TUMOR HYPOXIA | - |
dc.subject | SELECTIVE CYTOTOXINS | - |
dc.subject | IN-VITRO | - |
dc.subject | EXTRAVASCULAR TRANSPORT | - |
dc.subject | CANCER-CHEMOTHERAPY | - |
dc.subject | NITROGEN MUSTARDS | - |
dc.subject | BIOREDUCTIVE DRUG | - |
dc.subject | ELECTRON-TRANSFER | - |
dc.title | Radiolytic and cellular reduction of a novel hypoxia-activated cobalt(III) prodrug of a chloromethylbenzindoline DNA minor groove alkylator | - |
dc.type | Article | - |
dc.contributor.college | 융합생명공학부 | - |
dc.identifier.doi | 10.1016/J.BCP.2006.03.007 | - |
dc.author.google | Ahn, GO | - |
dc.author.google | Botting, KJ | - |
dc.author.google | Patterson, AV | - |
dc.author.google | Ware, DC | - |
dc.author.google | Tercel, M | - |
dc.author.google | Wilson, WR | - |
dc.relation.volume | 71 | - |
dc.relation.issue | 12 | - |
dc.relation.startpage | 1683 | - |
dc.relation.lastpage | 1694 | - |
dc.contributor.id | 10967338 | - |
dc.relation.journal | BIOCHEMICAL PHARMACOLOGY | - |
dc.relation.index | SCI급, SCOPUS 등재논문 | - |
dc.relation.sci | SCI | - |
dc.collections.name | Journal Papers | - |
dc.type.rims | ART | - |
dc.identifier.bibliographicCitation | BIOCHEMICAL PHARMACOLOGY, v.71, no.12, pp.1683 - 1694 | - |
dc.identifier.wosid | 000238056200003 | - |
dc.date.tcdate | 2019-01-01 | - |
dc.citation.endPage | 1694 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 1683 | - |
dc.citation.title | BIOCHEMICAL PHARMACOLOGY | - |
dc.citation.volume | 71 | - |
dc.contributor.affiliatedAuthor | Ahn, GO | - |
dc.identifier.scopusid | 2-s2.0-33646497001 | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.wostc | 50 | - |
dc.description.scptc | 49 | * |
dc.date.scptcdate | 2018-05-121 | * |
dc.type.docType | Article | - |
dc.subject.keywordPlus | MULTICELLULAR LAYER CULTURES | - |
dc.subject.keywordPlus | PREDICTS RADIATION RESPONSE | - |
dc.subject.keywordPlus | EXPLOITING TUMOR HYPOXIA | - |
dc.subject.keywordPlus | SELECTIVE CYTOTOXINS | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | EXTRAVASCULAR TRANSPORT | - |
dc.subject.keywordPlus | CANCER-CHEMOTHERAPY | - |
dc.subject.keywordPlus | NITROGEN MUSTARDS | - |
dc.subject.keywordPlus | BIOREDUCTIVE DRUG | - |
dc.subject.keywordPlus | ELECTRON-TRANSFER | - |
dc.subject.keywordAuthor | tumour hypoxia | - |
dc.subject.keywordAuthor | prodrug | - |
dc.subject.keywordAuthor | ionising radiation | - |
dc.subject.keywordAuthor | Co(III) complex | - |
dc.subject.keywordAuthor | CBI | - |
dc.subject.keywordAuthor | DNA minor groove alkylator | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
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