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Biological evaluation of both enantiomers of fluoro-thalidomide using human myeloma cell line H929 and others

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 t...

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Autores principales: Tokunaga, Etsuko, Akiyama, Hidehiko, Soloshonok, Vadim A., Inoue, Yuki, Hara, Hideaki, Shibata, Norio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538663/
https://www.ncbi.nlm.nih.gov/pubmed/28763493
http://dx.doi.org/10.1371/journal.pone.0182152
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author Tokunaga, Etsuko
Akiyama, Hidehiko
Soloshonok, Vadim A.
Inoue, Yuki
Hara, Hideaki
Shibata, Norio
author_facet Tokunaga, Etsuko
Akiyama, Hidehiko
Soloshonok, Vadim A.
Inoue, Yuki
Hara, Hideaki
Shibata, Norio
author_sort Tokunaga, Etsuko
collection PubMed
description 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.
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spelling pubmed-55386632017-08-07 Biological evaluation of both enantiomers of fluoro-thalidomide using human myeloma cell line H929 and others Tokunaga, Etsuko Akiyama, Hidehiko Soloshonok, Vadim A. Inoue, Yuki Hara, Hideaki Shibata, Norio PLoS One Research Article 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. Public Library of Science 2017-08-01 /pmc/articles/PMC5538663/ /pubmed/28763493 http://dx.doi.org/10.1371/journal.pone.0182152 Text en © 2017 Tokunaga et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Tokunaga, Etsuko
Akiyama, Hidehiko
Soloshonok, Vadim A.
Inoue, Yuki
Hara, Hideaki
Shibata, Norio
Biological evaluation of both enantiomers of fluoro-thalidomide using human myeloma cell line H929 and others
title Biological evaluation of both enantiomers of fluoro-thalidomide using human myeloma cell line H929 and others
title_full Biological evaluation of both enantiomers of fluoro-thalidomide using human myeloma cell line H929 and others
title_fullStr Biological evaluation of both enantiomers of fluoro-thalidomide using human myeloma cell line H929 and others
title_full_unstemmed Biological evaluation of both enantiomers of fluoro-thalidomide using human myeloma cell line H929 and others
title_short Biological evaluation of both enantiomers of fluoro-thalidomide using human myeloma cell line H929 and others
title_sort biological evaluation of both enantiomers of fluoro-thalidomide using human myeloma cell line h929 and others
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538663/
https://www.ncbi.nlm.nih.gov/pubmed/28763493
http://dx.doi.org/10.1371/journal.pone.0182152
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