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},
  author={Etsuko Tokunaga and Hidehiko Akiyama and Vadim A. Soloshonok and Yuki Inoue and Hideaki Hara and Norio Shibata},
  journal={PLoS ONE},
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… Expand
On the correlation of cereblon binding, fluorination and antiangiogenic properties of immunomodulatory drugs.
F fluorination is identified to correlate both with CRBN binding affinity and with antiangiogenic effects, but a correlation between the latter two phenomena is not found, indicating that the main target for the antiangIogenic effects of thalidomide analogs still remains to be identified. Expand
Understanding the Thalidomide Chirality in Biological Processes by the Self-disproportionation of Enantiomers
It is hypothesize that a fraction of thalidomide enantiomers epimerizes in vivo, followed by precipitation of racemic thalidmide in (R/S)-heterodimeric form, which means that racemicThalidomides is most likely removed from biological processes upon racemic precipitation in (S/S/R)/S-heterodermic form. Expand
Similar Safety Profile of the Enantiomeric N-Aminoalkyl Derivatives of Trans-2-Aminocyclohexan-1-ol Demonstrating Anticonvulsant Activity
The study indicated the similar safety profile of the enantiomeric N-aminoalkyl derivatives of trans-2-aminocyclohexan-1-ol, although in the previous studies both enantiomers differ in their biotransformation pathways and pharmacological activity. Expand
Synthesis of fluoro-functionalized diaryl-λ3-iodonium salts and their cytotoxicity against human lymphoma U937 cells
It was discovered that the ortho-fluoro-functionalized diaryliodonium salt reagents showed remarkable cytotoxicity in vitro, which led to synthesizing more compounds, previously unknown sterically demanding diarylionium salts having a pentafluorosulfanyl (SF5) functional group at the Ortho-position. Expand
Contribution of Organofluorine Compounds to Pharmaceuticals
This mini-review analyzes the prevalence of fluoro-pharmaceuticals in the market and categorizes them into several groups based on the chemotype of thefluoro-functional groups, their therapeutic purpose, and the presence of heterocycles and/or chirality to highlight the structural motifs, patterns, and promising trends in fluorine-based drug design. Expand
Andrographolide, isolated from Andrographis paniculata, induces apoptosis in monocytic leukemia and multiple myeloma cells via augmentation of reactive oxygen species production
Background: Andrographolide (Andro) is a diterpenoid component of the plant Andrographis paniculata that is known for its anti-tumor activity against a variety of cancer cells.   Methods: We studiedExpand
Fluorine-containing pharmaceuticals approved by the FDA in 2020: Synthesis and biological activity
  • Yingjie Yu, Aiyao Liu, +5 authors Jianlin Han
  • Medicine
  • 2021
Thirteen new fluorine-containing drugs, which have been granted approval by the US Food and Drug Administration in 2020, are profiled in this review, providing a spectrum of biological activity, medicinal chemistry discovery, and synthetic approaches. Expand
Repurposing Immunomodulatory Imide Drugs (IMiDs) in Neuropsychiatric and Neurodegenerative Disorders
The role of neuroinflammation is summarized in psychiatric disorders such as major depressive disorder, generalized anxiety disorder, post-traumatic stress disorder, and bipolar disorder, as well as in neurodegenerative disorders, and current research on the potential of immunomodulatory imide drugs (IMiDs) as a new treatment strategy for these disorders are introduced. Expand
Tailor-made amino acids in the design of small-molecule blockbuster drugs.
In the present article, 14 small-molecule drugs are profile, underscoring the breadth of structural variety of AAs applications in numerous therapeutic areas and providing spectrum of biological activity, medicinal chemistry discovery, and synthetic approaches. Expand
Internal chirality descriptors iR and iS and ire and isi. A proposed notation to extend the usefulness of the R/S system by retaining the sense of stereochemistry in cases of ligand ranking changes.
The proposed iR/iS notation could find profitable use in comparative studies where there is a need to avoid confusion arising from changing assignments due to priority rules or to expedite the ease of comprehension. Expand


Alpha-fluoro-substituted thalidomide analogues.
It is hypothesized that different biological properties are associated with each isomer of thalidomide, and chirally stable analogue 4 was non-cytotoxic at the tested concentrations and was found to be 830-fold more potent than thalidmide as TNF-alpha inhibitor. Expand
α-Fluoro-substituted thalidomide analogues
Thalidomide, (1), has made a remarkable comeback from its days of a sedative with teratogenic properties due to its ability to selectively inhibit TNF-α, a key pro-inflammatory cytokine and itsExpand
Antiangiogenic activity of N-substituted and tetrafluorinated thalidomide analogues.
The results support the further development and evaluation of novel thalidomide analogues as antiangiogenic agents and demonstrate antiproliferative action in human umbilical vein endothelial cells. Expand
Concise asymmetric synthesis of configurationally stable 4-trifluoromethyl thalidomide.
A reliable asymmetric approach is developed for preparation of hitherto unknown 4-trifluoromethyl-substituted thalidomide in (3S,4R) and (3R,4S) enantiomerically pure forms that may serve as useful lead compounds for the development of a new generation of thalidmide-based pharmaceuticals. Expand
Therapeutic Potential of Thalidomide and Its Analogues in the Treatment of Cancer.
  • G. Sherbet
  • Medicine, Biology
  • Anticancer research
  • 2015
The mode of action of thalidomides and their strategic utility in therapy are evaluated in the context of potential clinical benefits; they do exert teratogenic effects in animal models, although being effective at lower doses, the drugs seem to show comparatively manageable and reduced toxicity. Expand
Effect of 3-fluorothalidomide and 3-methylthalidomide enantiomers on tumor necrosis factor production and antitumor responses to the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA).
There is no advantage in using the nonracemizable thalidomide analogues to improve the antitumor activity of DMXAA, and no enantioselectivity was apparent. Expand
s-thalidomide has a greater effect on apoptosis than angiogenesis in a multiple myeloma cell line.
  • Wai M. Liu, S. Strauss, +5 authors J. Malpas
  • Biology, Medicine
  • The hematology journal : the official journal of the European Haematology Association
  • 2004
The data suggest that both angiogenic and apoptotic genes and proteins are affected by s- thalidomide, and a dramatic decrease in Bcl-2 expression with s-thalidomides suggests a possible enhancement of cytotoxic effect if combined with other cytot toxic agents. Expand
Thalidomide: current uses.
  • R. Powell
  • Medicine
  • BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
  • 1999
The recent trials of thalidomide in rheumatoid arthritis emphasise the problems with tolerability; an unacceptably high rate of adverse events led to the premature termination of these studies. Expand
Clinical Pharmacokinetics of Thalidomide
Thalidomide is a racemic glutamic acid derivative approved in the US for erythema nodosum leprosum, a complication of leprosy and its pharmacokinetics are not expected to change in patients with impaired liver or kidney function, and multiple-dose studies in cancer patients show pharmacokinetic comparable with those in healthy populations at similar dosages. Expand
Thalidomide metabolites in mice and patients with multiple myeloma.
  • J. Lu, B. Palmer, +4 authors L. Ching
  • Medicine
  • Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2003
It is suggested that thalidomide may act directly, down-regulating growth factors essential for multiple myeloma growth. Expand