The novel L-nucleoside analogue, 5-Fluorotroxacitabine, displays potent efficacy against acute myeloid leukemia

Bankar, Aniket; Siriwardena, Thirushi; Rizoska, Biljana; Rydergård, Christina; Kylefjord, Helen; Rraklli, Vilma; Eneroth, Anders; Pinho, Pedro; Norin, Stefan; Bylund, Johan; Moses, Sara; Bethell, Richard C.; Kavanagh, Simon; MacLean, Neil; Gronda, Marcela; Wang, Xiaoming; Hurren, Rose; Minden, Mark D.; Targett-Adams, Paul; Schimmer, Aaron D.; Albertella, Mark R.

doi:10.3324/haematol.2019.226795

Cited by 4 publications

(4 citation statements)

References 8 publications

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“…4 A number of other L-nucleoside derivatives have been prepared as antiviral agents. These include the 5-fluoro analogue of lamivudine, emtricitabine (2, β-L-2′,3′-dideoxy-3′-thia-5-fluorocytidine, FTC) for the treatment of HIV infections, the β-L-thymidine (3, telbivudine), clevudine (4), and elvucitabine (5) analogues are approved antiviral drugs against HBV, as well as maribavir (6), another L-nucleoside against cytomegalovirus infection. 5…”

Section: Introductionmentioning

confidence: 99%

“…Troxacitabine ( 7 , Figure ) is the first compound with l isomerism that has shown activity against solid tumors and leukemia. Another example is its 5-fluoro analogue, 5-fluorotroxacitabine ( 8 ), which has shown in vitro activity against acute myeloid leukemia …”

Section: Introductionmentioning

confidence: 99%

“…Another example is its 5-fluoro analogue, 5-fluorotroxacitabine (8), which has shown in vitro activity against acute myeloid leukemia. 6 This article is licensed under CC-BY-NC-ND 4.0 On the other hand, L-nucleosides can be used as monomers to prepare L-oligonucleotides. Although L-oligonucleotides are not present in nature, they can be easily prepared synthetically in the laboratory.…”

Section: Introductionmentioning

confidence: 99%

“…Another example is its 5-fluoro analogue, 5-fluorotroxacitabine ( 8 ), which has shown in vitro activity against acute myeloid leukemia. 6 …”

Section: Introductionmentioning

confidence: 99%

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Synthesis of 2′-O-Methyl/2′-O-MOE-L-Nucleoside Derivatives and Their Applications: Preparation of G-Quadruplexes, Their Characterization, and Stability Studies

Martín-Nieves,

Menéndez-Méndez,

Fàbrega

et al. 2023

ACS Omega

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Nucleosides and their analogues constitute an important family of molecules with potential antiviral and antiproliferative activity. The enantiomers of natural nucleosides, l-nucleoside derivatives, which have comparable biological activity but more favorable toxicological properties and greater metabolic stability than d-nucleosides, have emerged as a new class of therapeutic agents. Furthermore, l-nucleosides can be used as a building block to prepare l-oligonucleotides, which have identical physical properties in terms of solubility, hybridization kinetics, and duplex thermal stability as d-oligonucleotides but completely orthogonal in nature. Consequently, they are resistant to nuclease degradation, nontoxic, and immunologically passive, which are desirable properties for biomedical applications. Herein, we describe the synthesis of several 2′-O-methyl/2′-O-MOE-l-nucleoside pyrimidine derivatives and their incorporation into G-rich oligonucleotides. Finally, we evaluated the stability and resistance against nucleases of these new G-quadruplexes, demonstrating the potential of the l-nucleosides described in this work in providing enhanced nuclease resistance with a minimal impact in the nucleic acid structural properties.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Another example is its 5-fluoro analogue, 5-fluorotroxacitabine ( 8 ), which has shown in vitro activity against acute myeloid leukemia. 6 …”

Section: Introductionmentioning

confidence: 99%

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Synthesis of 2′-O-Methyl/2′-O-MOE-L-Nucleoside Derivatives and Their Applications: Preparation of G-Quadruplexes, Their Characterization, and Stability Studies

Martín-Nieves,

Menéndez-Méndez,

Fàbrega

et al. 2023

ACS Omega

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Design, Synthesis, and Biological Activity of l-1′-Homologated Adenosine Derivatives

Nguyen

et al. 2022

ACS Med. Chem. Lett.

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On the basis of the previously reported polypharmacological profile of truncated D-1′-homologated adenosine derivatives [J. Med. Chem. 2020, 63, 16012], the Lnucleoside analogues were synthesized using computer-aided design and evaluated for biological activity. The target molecules were synthesized from D-ribose via the key intramolecular cyclization of the monotosylate and Mitsunobu condensation. The peroxisome proliferator-activated receptor (PPAR) binding activities of L-nucleoside analogue 2d (K i = 4.3 μM for PPARγ and 1.0 μM for PPARδ) were significantly improved in comparison with those of the D-nucleoside compound 1 (11.9 and 2.7 μM, respectively). In addition, the L-nucleosides showed more potent adiponectin-secretion-promoting activity than the D-nucleoside analogues.

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Advances in Therapeutic L-Nucleosides and L-Nucleic Acids with Unusual Handedness

Dantsu

Zhang

2021

Genes

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Nucleic-acid-based small molecule and oligonucleotide therapies are attractive topics due to their potential for effective target of disease-related modules and specific control of disease gene expression. As the non-naturally occurring biomolecules, modified DNA/RNA nucleoside and oligonucleotide analogues composed of L-(deoxy)riboses, have been designed and applied as innovative therapeutics with superior plasma stability, weakened cytotoxicity, and inexistent immunogenicity. Although all the chiral centers in the backbone are mirror converted from the natural D-nucleic acids, L-nucleic acids are equipped with the same nucleobases (A, G, C and U or T), which are critical to maintain the programmability and form adaptable tertiary structures for target binding. The types of L-nucleic acid drugs are increasingly varied, from chemically modified nucleoside analogues that interact with pathogenic polymerases to nanoparticles containing hundreds of repeating L-nucleotides that circulate durably in vivo. This article mainly reviews three different aspects of L-nucleic acid therapies, including pharmacological L-nucleosides, Spiegelmers as specific target-binding aptamers, and L-nanostructures as effective drug-delivery devices.

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The novel L-nucleoside analogue, 5-Fluorotroxacitabine, displays potent efficacy against acute myeloid leukemia

Cited by 4 publications

References 8 publications

Synthesis of 2′-O-Methyl/2′-O-MOE-L-Nucleoside Derivatives and Their Applications: Preparation of G-Quadruplexes, Their Characterization, and Stability Studies

Synthesis of 2′-O-Methyl/2′-O-MOE-L-Nucleoside Derivatives and Their Applications: Preparation of G-Quadruplexes, Their Characterization, and Stability Studies

Design, Synthesis, and Biological Activity of l-1′-Homologated Adenosine Derivatives

Advances in Therapeutic L-Nucleosides and L-Nucleic Acids with Unusual Handedness

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