13030-62-1Relevant academic research and scientific papers
Synthesis of nucleoside-based antiviral drugs in ionic liquids
Kumar, Vineet,Malhotra, Sanjay V.
, p. 5640 - 5642 (2008)
Nucleoside-based antiviral drugs have been synthesized using imidazolium-based ionic liquids as reaction medium. The ionic liquids were proved to be better solvents for all the nucleoside in terms of solubility and reaction medium as compared to conventional molecular solvents.
Photocycloaddition of deoxyuridines to 2,3-dimethyl-2-butene
Haga,Ishikawa,Takayanagi,Ogura
, p. 728 - 737 (1994)
Direct and ketone (acetone or acetophenone)-sensitized photocycloaddition of 2,3-dimethyl-2-butene fo 2'-deoxyuridine (1a), thymidine (1b), 5-fluoro-2'-deoxyuridine (1c), and their 3',5'-di- O-acetyl derivatives 1d-1f by near-UV irradiation have been studied. The triplet excited state of the nucleosides was found to be the major intermediate by the triplet quenching technique. From the respective reactants, a pair of diastereomeric products having a cyclobutane ring were isolated. The absolute configuration of the bridgehead carbon atoms was identified by X-ray crystallographic analyses with two of them as (1R, 6R)-isomer 3a and (1S, 6S)-isomer 2b and by 1H NMH. The conformations of the glycosyl bond, the pyrimidine ring, and the sugar portion in solution were identified by 1H NMR and compared with the ones in the crystalline state.
An efficient and general synthesis of 5'-esters of 2',3'-didehydro-2',3'-dideoxynucleosides: A facile opening of 2',3'-orthoacetates of ribonucleosides followed by reductive elimination of the halogenoacetates
Talekar,Coe,Walker
, p. 303 - 306 (1993)
A three-step reaction sequence from a ribonucleoside to give the corresponding 5'-O-acyl-2',3'-didehydro-2',3'-dideoxynucleoside is described. The key intermediate is the bromoacetate, made by reaction of the 2',3'-methoxyethylidine nucleoside with acetyl bromide. Reductive elimination of the bromoacetate using a zinc-copper couple furnishes the desired compounds in good overall yield.
5-iodo-4-thio-2′-deoxyuridine as a sensitizer of X-ray induced cancer cell killing
Makurat, Samanta,Spisz, Paulina,Kozak, Witold,Rak, Janusz,Zdrowowicz, Magdalena
, (2019)
Nucleosides, especially pyrimidines modified in the C5-position, can act as radiosensitizers via a mechanism that involves their enzymatic triphosphorylation, incorporation into DNA, and a subsequent dissociative electron attachment (DEA) process. In this paper, we report 5-iodo-4-thio-2′-deoxyuridine (ISdU) as a compound that can effectively lead to ionizing radiation (IR)-induced cellular death, which is proven by a clonogenic assay. The test revealed that the survival of cells, pre-treated with 10 or 100 μM solution of ISdU and exposed to 0.5 Gy of IR, was reduced from 78.4% (for non-treated culture) to 67.7% and to 59.8%, respectively. For a somewhat higher dose of 1 Gy, the surviving fraction was reduced from 68.2% to 54.9% and to 40.8% for incubation with 10 or 100 μM ISdU, respectively. The cytometric analysis of histone H2A.X phosphorylation showed that the radiosensitizing effect of ISdU was associated, at least in part, with the formation of double-strand breaks. Moreover, the cytotoxic test against the MCF-7 breast cancer cell line and human dermal fibroblasts (HDFa line) confirmed low cytotoxic activity of ISdU. Based on the results of steady state radiolysis of ISdU with a dose of 140 Gy and quantum chemical calculations explaining the origin of the MS detected radioproducts, the molecular mechanism of sensitization by ISdU was proposed. In conclusion, we found ISdU to be a potential radiosensitizer that could improve anticancer radiotherapy.
Modified nucleotides as substrates of terminal deoxynucleotidyl transferase
Tauraite, Daiva,Jakubovska, Jevgenija,Dabu?inskaite, Julija,Bratchikov, Maksim,Me?kys, Rolandas
, (2017)
The synthesis of novel modified nucleotides and their incorporation into DNA sequences opens many possibilities to change the chemical properties of oligonucleotides (ONs), and, therefore, broaden the field of practical applications of modified DNA. The chemical synthesis of nucleotide derivatives, including ones bearing thio-, hydrazino-, cyano- and carboxy groups as well as 2-pyridone nucleobase-containing nucleotides was carried out. The prepared compounds were tested as substrates of terminal deoxynucleotidyl transferase (TdT). The nucleotides containing N4-aminocytosine, 4-thiouracil as well as 2-pyridone, 4-chloro- and 4-bromo-2-pyridone as a nucleobase were accepted by TdT, thus allowing enzymatic synthesis of 3′-terminally modified ONs. The successful UV-induced cross-linking of 4-thiouracil-containing ONs to TdT was carried out. Enzymatic post-synthetic 3′-modification of ONs with various photo- and chemically-reactive groups opens novel possibilities for future applications, especially in analysis of the mechanisms of polymerases and the development of photo-labels, sensors, and self-assembling structures.
Synthesis and biological activity of 5-(trifluoromethyl)- and 5-(pentafluorethyl)pyrimidine nucleoside analogues
Lin,Gao
, p. 598 - 601 (1983)
Various 5-substituted perfluoroalkylpyrimidine nucleoside analogues have been synthesized, and their biological activity against L1210, S-180, Vero cells, and herpes simplex virus type 1 (HSV-1) was evaluated. The 5-trifluoromethyl derivatives, 7 and 9, showed significant antiviral activity against HSV-1 with ED50 values of 7 and 5 μM, respectively. In addition, the unblocked nucleoside 9 was found to be about 64-fold less toxic to the host Vero cells and gave a favorable therapeutic index of 64 against HSV-1 in vitro.
5-Ethynyl-2′-deoxyuridine as a molecular probe of cell proliferation for high-content siRNA screening assay by "click" chemistry
Chen, Miaojuan,Qu, Dezhong,Chi, Weilin,Wang, Wei,Ren, Xiaoshuai,Cong, Shujie,Liang, Peizhou,Feng, Shipeng,Zhang, Biliang
, p. 1702 - 1710 (2011)
Labelling and identification of proliferating cells is important for the study of physiological or pathological processes in high-content screening (HCS) assays. Here we describe ethynyl deoxyuridine (EdU) as a biomarker for the assessment of cell proliferation and clearly demonstrate the feasibility of the EdU-labelling method for use in HCS assays. EdU detection is highly robust, reproducible, technically simple, and well suited for automated segmentation, which provides an excellent alternative for setting up multiplexed HCS assays of siRNA, miRNA and small-molecule libraries.
A synergistic synthetic and computational insights towards anomerization of N-nitro pyrimidine nucleosides using fluorinating agents
Bayach, Imene,Khalil, Ahmed,Mathé, Christophe
, (2020)
DAST and Deoxofluor are usually used for nucleophilic fluorination of nucleosides via SN1 or SN2 mechanism. DAST and Deoxo-fluor could enhance anomerization of N-substituted thymidine and 2′-deoxyuridine in dichloromethane into the more stable and favored α-anomers due to in-situ liberation of HF. This is strongly supported by computational calculations based on the density functional theory, that were performed to rationalize energy stability and electronic properties of both anomers in order to provide further insights into the proposed mechanism.
4 -thiouracil deoxynucleoside phosphate and application thereof in antiviral medicine
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Paragraph 0031-0034, (2021/10/16)
The invention discloses 4 -thiouracil deoxynucleoside phosphate and a structural formula thereof. Q06, discovery of new drug molecules not only has a new choice for treating hepatitis B, but also has important significance for developing more ideal hepatitis B drugs for treating hepatitis B.
NMR studies on 4-thio-5-furan-modified and 4-thio-5-thiophene-modified nucleosides
Zhang, Xiao-Hui,Xu, Yao-Zhong
, p. 887 - 892 (2016/10/24)
Systematic NMR characterization of 4-thio-5-furan-pyrimidine nucleosides or 4-thio-5-thiophene-pyrimidine nucleosides (ribonucleosides and 2′-deoxynucleosides) was performed. All proton and carbon signals of 4-thio-5-thiophene-ribouridine and related analogues were unambiguously assigned. The orientations of the base (4-thiouridine or its deoxy analogue) relative to the ring (furan or thiophene) are explored by a NMR approach and further supported by X-ray crystallographic studies. The procedures presented here would be applicable to other modified nucleosides and nucleotides. Copyright
