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dc.contributor.authorTokunaga, Etsuko
dc.contributor.authorAkiyama, Hidehiko
dc.contributor.authorSoloshonok, Vadym Anatolievch
dc.contributor.authorInoue, Yuki
dc.contributor.authorHara, Hideaki
dc.contributor.authorShibata, Norio
dc.date.accessioned2019-05-08T07:55:01Z
dc.date.available2019-05-08T07:55:01Z
dc.date.issued2017-08-01
dc.identifier.citationPlos One 12(8) : (2017) // Article ID e0182152es_ES
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10810/32684
dc.description.abstractOver the last few years, thalidomide has become one of the most important anti-tumour drugs for the treatment of relapsed-refractory multiple myeloma. However, besides its undesirable teratogenic side effect, its configurational instability critically limits any further therapeutic improvements of this drug. In 1999, we developed fluoro-thalidomide which is a bioisostere of thalidomide, but, in sharp contrast to the latter, it is configurationally stable and readily available in both enantiomeric forms. The biological activity of fluoro-thalidomide however, still remains virtually unstudied, with the exception that fluoro-thalidomide is not teratogenic. Herein, we report the first biological evaluation of fluoro-thalidomide in racemic and in both (R)- and (S)-enantiomerically pure forms against (in vitro) H929 cells of multiple myeloma (MM) using an annexin V assay. We demonstrate that all fluoro-thalidomides inhibited the growth of H929 MM cells without any in-vivo activation. Furthermore, we report that the enantiomeric forms of fluoro-thalidomide display different anti-tumour activities, with the (S)-enantiomer being noticeably more potent. The angiogenesis of fluoro-thalidomides is also investigated and compared to thalidomide. The data obtained in this study paves the way towards novel pharmaceutical research on fluoro-thalidomides.es_ES
dc.description.sponsorshipThis research is (partially) supported by Kobayashi International Foundation, a specific research grant from Takeda Science Foundation, Japan, the Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from Japan Agency for Medical Research and Development (AMED), the Advanced Catalytic Transformation (ACT-C) from the Japan Science and Technology (JST) Agency. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Mr. Okiya Matsubara for kind assistance with the submission of this manuscript, and Mr. Hiroki Doi for his help of biological assay. Funding Statement: This research is (partially) supported by Kobayashi International Foundation, a specific research grant from Takeda Science Foundation, Japan, the Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from Japan Agency for Medical Research and Development (AMED), the Advanced Catalytic Transformation (ACT-C) from the Japan Science and Technology (JST) Agency.es_ES
dc.language.isoenges_ES
dc.publisherPublic Library Sciencees_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subjectcytochrome-P450 3A enzymeses_ES
dc.subjectself-disproportionationes_ES
dc.subjectmultiple-myelomaes_ES
dc.subjectin-vitroes_ES
dc.subjectachiral chromatographyes_ES
dc.subjectoptical purificationses_ES
dc.subjectasymmetric-synthesises_ES
dc.subjectanalogses_ES
dc.subjectangiogenesises_ES
dc.subjectapoptosises_ES
dc.titleBiological Evaluation of Both Enantiomers of Fluoro-Thalidomide Using Human Myeloma Cell Line H929 and Otherses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.holderThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Attribution 4.0 International (CC BY 4.0)es_ES
dc.rights.holderAtribución 3.0 España*
dc.relation.publisherversionhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182152es_ES
dc.identifier.doi10.1371/journal.pone.0182152
dc.departamentoesQuímica orgánica Ies_ES
dc.departamentoeuKimika organikoa Ies_ES


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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Attribution 4.0 International (CC BY 4.0)