Biological Evaluation of Both Enantiomers of Fluoro-Thalidomide Using Human Myeloma Cell Line H929 and Others
dc.contributor.author | Tokunaga, Etsuko | |
dc.contributor.author | Akiyama, Hidehiko | |
dc.contributor.author | Soloshonok, Vadym Anatolievch ![]() | |
dc.contributor.author | Inoue, Yuki | |
dc.contributor.author | Hara, Hideaki | |
dc.contributor.author | Shibata, Norio | |
dc.date.accessioned | 2019-05-08T07:55:01Z | |
dc.date.available | 2019-05-08T07:55:01Z | |
dc.date.issued | 2017-08-01 | |
dc.identifier.citation | Plos One 12(8) : (2017) // Article ID e0182152 | es_ES |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/10810/32684 | |
dc.description.abstract | Over 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.sponsorship | 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. 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.iso | eng | es_ES |
dc.publisher | Public Library Science | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | cytochrome-P450 3A enzymes | es_ES |
dc.subject | self-disproportionation | es_ES |
dc.subject | multiple-myeloma | es_ES |
dc.subject | in-vitro | es_ES |
dc.subject | achiral chromatography | es_ES |
dc.subject | optical purifications | es_ES |
dc.subject | asymmetric-synthesis | es_ES |
dc.subject | analogs | es_ES |
dc.subject | angiogenesis | es_ES |
dc.subject | apoptosis | es_ES |
dc.title | Biological Evaluation of Both Enantiomers of Fluoro-Thalidomide Using Human Myeloma Cell Line H929 and Others | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | 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) | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182152 | es_ES |
dc.identifier.doi | 10.1371/journal.pone.0182152 | |
dc.departamentoes | Química orgánica I | es_ES |
dc.departamentoeu | Kimika organikoa I | es_ES |
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