Synthesis, Biological Evaluation, and Radioiodination of Halogenated closo-Carboranylthymidine Analogues
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Tiwari, Rohit | - |
dc.contributor.author | Toppino, Antonio | - |
dc.contributor.author | Agarwal, Hitesh K. | - |
dc.contributor.author | Huo, Tianyao | - |
dc.contributor.author | Byun, Youngjoo | - |
dc.contributor.author | Gallucci, Judith | - |
dc.contributor.author | Hasabenaby, Sherifa | - |
dc.contributor.author | Khalil, Ahmed | - |
dc.contributor.author | Goudah, Ayman | - |
dc.contributor.author | Baiocchi, Robert A. | - |
dc.contributor.author | Darby, Michael V. | - |
dc.contributor.author | Barth, Rolf F. | - |
dc.contributor.author | Tjarks, Werner | - |
dc.date.accessioned | 2021-09-06T23:13:10Z | - |
dc.date.available | 2021-09-06T23:13:10Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2012-01-02 | - |
dc.identifier.issn | 0020-1669 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/109104 | - |
dc.description.abstract | The synthesis and initial biological evaluation of 3-carboranylthymidine analogues (3CTAs) that are (radio)halogenated at the closo-carborane cluster are described. Radiohalogenated 3CTAs have the potential to be used in the radiotherapy and imaging of cancer because they may be selectively entrapped in tumor cells through monophosphorylation by human thymidine kinase 1 (hTK1). Two strategies for the synthesis of a I-127-labeled form of a specific 3CTA, previously designated as N5, are described: (1) direct iodination of N5 with iodine monochloride and aluminum chloride to obtain N5-I-127 and (2) initial monoiodination of o-carborane to 9-iodo-o-carborane followed by its functionalization to N5-I-127. The former strategy produced N5-I-127 in low yields along with di-, tri-, and tetraiodinated N5 as well as decomposition products, whereas the latter method produced only N5-I-127 in high yields. N5-I-127 was subjected to nudeophilic halogen- and isotope-exchange reactions using Na-79/Br-81 and (NaI)-I-125, respectively, in the presence of Herrmann's catalyst to obtain N5-(79)/Br-81 and N5-I-125, respectively. Two intermediate products formed using the second strategy, 1-(tert-butyldimethylsilyl)-9-iodo-o-carborane and 1-(tert-butyldimethylsilyl)-12-iodo-o-carborane, were subjected to X-ray diffraction studies to confirm that substitution at a single carbon atom of 9-iodo-o-carborane resulted in the formation of two structural isomers. To the best of our knowledge, this is the first report of halogen- and isotope-exchange reactions of B-halocarboranes that have been conjugated to a complex biomolecule. Human TK1 phosphorylation rates of NS, N5-I-127, and N5-(79)/Br-81 ranged from 38.0% to 29.6% relative to that of thymidine, the endogenous hTK1 substrate. The in vitro uptake of NS, N5-I-127, and NS-(79)/Br-81 in L929 TK1(+) cells was 2.0, 1.8, and 1.4 times greater than that in L929 TK1() cells. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.subject | NEUTRON-CAPTURE THERAPY | - |
dc.subject | FLUORINATED THYMIDINE DERIVATIVES | - |
dc.subject | IMAGING CELL-PROLIFERATION | - |
dc.subject | BRAIN-TUMORS | - |
dc.subject | ORGANOMETALLIC TECHNETIUM | - |
dc.subject | CARBORANE DERIVATIVES | - |
dc.subject | QUATERNARY STRUCTURE | - |
dc.subject | MOLECULAR STRUCTURE | - |
dc.subject | SUBSTRATE ACTIVITY | - |
dc.subject | ISOTOPIC EXCHANGE | - |
dc.title | Synthesis, Biological Evaluation, and Radioiodination of Halogenated closo-Carboranylthymidine Analogues | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Byun, Youngjoo | - |
dc.identifier.doi | 10.1021/ic202150b | - |
dc.identifier.scopusid | 2-s2.0-84855408055 | - |
dc.identifier.wosid | 000298712000079 | - |
dc.identifier.bibliographicCitation | INORGANIC CHEMISTRY, v.51, no.1, pp.629 - 639 | - |
dc.relation.isPartOf | INORGANIC CHEMISTRY | - |
dc.citation.title | INORGANIC CHEMISTRY | - |
dc.citation.volume | 51 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 629 | - |
dc.citation.endPage | 639 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Inorganic & Nuclear | - |
dc.subject.keywordPlus | NEUTRON-CAPTURE THERAPY | - |
dc.subject.keywordPlus | FLUORINATED THYMIDINE DERIVATIVES | - |
dc.subject.keywordPlus | IMAGING CELL-PROLIFERATION | - |
dc.subject.keywordPlus | BRAIN-TUMORS | - |
dc.subject.keywordPlus | ORGANOMETALLIC TECHNETIUM | - |
dc.subject.keywordPlus | CARBORANE DERIVATIVES | - |
dc.subject.keywordPlus | QUATERNARY STRUCTURE | - |
dc.subject.keywordPlus | MOLECULAR STRUCTURE | - |
dc.subject.keywordPlus | SUBSTRATE ACTIVITY | - |
dc.subject.keywordPlus | ISOTOPIC EXCHANGE | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
145 Anam-ro, Seongbuk-gu, Seoul, 02841, Korea+82-2-3290-2963
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.