7236-57-9Relevant academic research and scientific papers
4 - Thiodeoxythymidine derivative and anti-hepatitis B virus pharmaceutical application thereof
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, (2021/10/05)
4 - Thio-deoxythymidine derivatives and anti-hepatitis B virus pharmaceutical applications thereof are disclosed. The invention provides 4 - thiodeoxythymidine derivative or a pharmaceutically acceptable salt thereof, and the structure is shown in structural formula I or structural formula II. An in-vitro cytotoxicity test and an in-vitro anti HBV virus pharmacodynamic test proves 4 - thiodeoxythymidine derivative or a pharmaceutically acceptable salt thereof has anti HBV activity, has an anti-hepatitis B drug development prospect and provides a potential choice for treating viral hepatitis.
Exploring the binding of 4-thiothymidine with human serum albumin by spectroscopy, atomic force microscopy, and molecular modeling methods
Zhang, Juling,Gu, Huaimin,Zhang, Xiaohui
, p. 102 - 111 (2014/01/17)
The interaction of 4-thiothymidine (S4TdR) with human serum albumin (HSA) was studied by equilibrium dialysis under normal physiological conditions. In this work, the mechanism of the interaction between S 4TdR and human serum albumin (HSA) was exploited by fluorescence, UV, CD circular, and SERS spectroscopic. Fluorescence and UV spectroscopy suggest that HSA intensities are significantly decreased when adding S4TdR to HAS, and the quenching mechanism of the fluorescence is static. Also, the ΔG, ΔH, and ΔS values across temperature indicated that hydrophobic interaction was the predominant binding force. The CD circular results show that there is little change in the secondary structure of HSA except the environment of amino acid changes when adding S4TdR to HSA. The surface-enhanced Raman scattering (SERS) shows that the interaction between S4TdR and HSA can be achieved through different binding sites which are probably located in the II A and III A hydrophobic pockets of HSA which correspond to Sudlow's I and II binding sites. In addition, the molecular modeling displays that S4TdR-HSA complex is stabilized by hydrophobic forces, which result from amino acid residues. The atomic force microscopy results revealed that the single HSA molecular dimensions were larger after interaction of 4-thiothymidine. This work would be useful to understand the state of the transportation, distribution, and metabolism of the anticancer drugs in the human body, and it could provide a useful biochemistry parameter for the development of new anti-cancer drugs and research of pharmacology mechanisms.
Systematic assignment of NMR spectra of 5-substituted-4-thiopyrimidine nucleosides
Zhang, Xiaohui,Wang, Jian,Xu, Yao-Zhong
, p. 523 - 529 (2013/09/02)
Unambiguous characterization of 5-substituted-4-thiopyrimidine nucleosides (ribonucleosides and 2'-deoxynucleosides) was performed using NMR spectroscopy. Assignments of all proton and carbon signals of 5-bromo-4-thiouridine and related nucleosides were systematically carried out and firmly established by COSY and HMQC techniques. The NMR data of various 4-thiopyrimidine nucleosides are compared, and the key contributing factors discussed. The approach presented here is applicable to other modified nucleosides and nucleotides, as well as nucleobases. Copyright
NMR and UV studies of 4-thio-2′-deoxyuridine and its derivatives
Zhang, Xiaohui,Xu, Yao-Zhong
, p. 5655 - 5664 (2011/09/20)
5-Substituted-4-thio-2'-deoxyuridine nucleosides have been chemically synthesized and studied by NMR and UV spectroscopy. The results have been analyzed and discussed in connection with the previous data. The imino proton signal and the carbon signal of the thiocarbonyl group in the 5-substituted-4-thio-2'-deoxyuridines were found to be at much lower field, offering a potential for monitoring these modified bases at the DNA level. All 4-thionucleosides have strong absorptions at around 340 nm and consequently would be useful as potential UVA-induced anticancer agents.
Convenient intermediates for the preparation of C-4 modified derivatives of pyrimidine nucleosides
Miah, Anwar,Reese, Colin B.,Song, Quanlai
, p. 53 - 65 (2007/10/03)
4-(4-Nitrophenoxy)-1-(β-D-ribofuranosyl)pyrimidin-2(1H)-one 15, 5- methyl-4-(1,2,4-triazol-1-yl)-1-(β-D-2-deoxyribofuranosyl)pyrimidin-2(1H)- one 7a and 4-(4-nitrophenoxy)-1-(βD-2-deoxyribofuranosyl)pyrimidin-2(1H)- one 17a, respectively, have been prepared and are recommended as reactive intermediates for the preparation of derivatives of uridine, thymidine and 2'-deoxyuridine which are modified at C-4.
Simple synthesis of 4-thiothymidine, 4-thiouridine and 6-thio-2′-deoxyguanosine
Xu, Yao-Zhong,Zheng, Qinguo,Swann, Peter F.
, p. 2817 - 2820 (2007/10/02)
4-triazolo-pyrimidine nucleosides and 6-O-(mesitylenesulfonyl)-2′-deoxyguanosine, when treated with thiolacetic acid at room temperature, gave the corresponding 4-thiopyrimidine nucleosides and 6-thio-2′-deoxyguanosine with high yields (86-93%). Possible mechanisms are discussed.
Synthesis and in vitro evaluation of some modified 4-thiopyrimidine nucleosides for prevention or reversal of AIDS-associated neurological disorders
Palomino,Meltsner,Kessel,Horwitz
, p. 258 - 263 (2007/10/02)
Oxygen-sulfur exchange at the C-4 carbonyl of several modified pyrimidine, including 3'-azido-3'-deoxythymidine (AZT), is described in an effort to enhance the lipophilicity and, thereby, the delivery to the central nervous system of the sulfur analogues without compromising the anti-HIV activities of the parental structures. Preparation of 3'-azido-3'-deoxy-4-thiothymidine (3) proceeded from 4-thiothymidine (1) and utilized the same methodology developed for the initial synthesis of AZT. Thiation of 2',3'-didehydro-3'-deoxythymidine (4a) and 2',3'-didehydro-2',3'-dideoxyuridine (4c) was carried out with Lawesson's reagent on the corresponding 5'-O-benzoate esters, 4b and 4d, to give 5 a and 5c, respectively. The latter, on alkaline hydrolysis, gave 2',3'-didehydro-3'-deoxy-4-thiothymidine (5b) and 2',3'-didehydro-2',3'-dideoxyuridine (5d), respectively. The same series of reactions were applied to the 5'-O-benzoate esters of 2',3'-dideoxyuridine (6a) and 3'-deoxythymidine (6b) to give 2',3'-dideoxy-4-thiouridine (7d) and 3'-deoxy-4-thiothymidine (7b), respectively. Characterization of the saturated and unsaturated thionucleosides included mass spectrometric studies. Under electron impact conditions, the thiated analogues gave more intensive parent ions than the corresponding oxygen precursors. The lipophilicity of thymidine and the 3'-deoxythymidine derivatives are enhanced significantly, as indicated, by increases in corresponding P values (1-octanol-0.1 M sodium phosphate) upon replacement of the 4-carbonyl oxygens by sulfur. Compounds 5b, 5d, 7b, and 7d were evaluated for their effects on HIV-induced cytopathogenicity of MT-2 and CEM cells. Only 5b and 7b were moderately active in protecting both cell lines against the cytolytic effect of HIV. The inhibitory effects of analogous 5b, 5d, 7b, and 7d on thymidine phosphorylation by rabbit thymus thymidine kinase were evaluated. Only 3 showed moderate affinity (K(i) = 54 μM) for the enzyme. The generally weak anti-HIV activities of the remaining thio analogues are consistent with correspondingly low susceptibilities to thymidine kinase phosphorylation as estimated from the respective K(i) values of the synthetic nucleosides. However, the phosphorylation of the 5'-monophosphate derivatives to their respective 5'-triphosphates must also be considered in connection with the weak in vitro anti-HIV effects of these thiated compounds.
