65499-40-3Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of novel C5-modified pyrimidine ribofuranonucleosides as potential antitumor or/and antiviral agents
Alexouli, Tania,Andrei, Graciela,Giannakas, Christos,Kollatos, Nikolaos,Komiotis, Dimitri,Manta, Stella,Mitsos, Christos,Panagiotopoulou, Aggeliki,Schols, Dominique,Tzioumaki, Niki
, p. 368 - 384 (2020/04/17)
Background: Nucleoside analogues are well-known antitumor, antiviral, and chemotherapeutic agents. Alterations on both their sugar and the heterocyclic parts may lead to significant changes in the spectrum of their biological activity and the degree of selective toxicity, as well as in their physicochemical properties. Method: C5-arylalkynyl-β-D-ribofuranonucleosides 3-6, 3?-deoxy 12-15, 3?-deoxy-3?-C-methyl-β-D-ribofurananucleosides 18-21 and 2?-deoxy-β-D-ribofuranonucleosides 23-26 of uracil, were synthesized using a one-step Sonogashira reaction under microwave irradiation and subsequent deprotection. Results: All newly synthesized nucleosides were tested for their antitumor or antiviral activity. Moderate cytostatic activity against cervix carcinoma (HeLa), murine leukemia (L1210) and human lymphocyte (CEM) tumor cell lines was displayed by the protected 3?-deoxy derivatives 12b, 12c, 12d, and the 3?-deoxy-3?-methyl 18a, 18b, 18c. The antiviral evaluation revealed appreciable activity against Coxsackie virus B4, Respiratory syncytial virus, Yellow Fever Virus and Human Coronavirus (229E) for the 3?-deoxy compounds 12b, 14, and the 3?-deoxy-3?-methyl 18a, 18c, 18d, accompanied by low cytotoxicity. Conclusion: This report describes the total and facile synthesis of modified furanononucleosides of uracil, with alterations on both the sugar and the heterocyclic portions. Compounds 12b, 14 and 18a,c,d showed noticeable antiviral activity against a series of RNA viruses and merit further biological and structural optimization investigations.
Visibly Emitting Thiazolyl-Uridine Analogues as Promising Fluorescent Probes
Li, Jinsi,Fang, Xuerong,Ming, Xin
, p. 4602 - 4610 (2020/05/01)
Microenvironment-sensitive fluorescent (ESF) nucleosides are powerful tools for nucleic acid research. The new 5-substituted uridine analogues are synthesized, which comprise a 4H-cyclopenta[d]thiazole ring obtained by the Hantzsch synthesis reaction of 5-thioamide-uridine with aromatic α-bromocarbonyl compounds. The emission maximum of new compounds is in the visible region. They exhibit strong solvent- A nd pH-dependent fluorescent properties, indicating their promising ability to be fluorescent probes.
Stereoselective Synthesis of Highly Functionalized Arabinosyl Nucleosides through Application of an N-Nitro Protecting Group
Hilko, David H.,Bornaghi, Laurent F.,Poulsen, Sally-Ann
, p. 11944 - 11955 (2018/09/25)
2′-Deoxy-2′,5-disubstituted arabinosyl uridine derivatives bearing a halogen (Cl, Br or I) at C2′ and an ethynyl group at C5 have been synthesized in 6 steps from 2′,3′,5′-tri-O-acetyl-5-iodo-uridine in overall yields of 61% (compound 3, Cl), 47% (compound 4, Br), and 19% (compound 5, I). Stabilization of a 2′-O-triflyl leaving group intermediate to overcome spontaneous intramolecular 2,2′-anhydro uridine formation was pivotal to the synthesis. Specifically, to favor SN2 reaction with a halogen nucleophile over intramolecular cyclization, the nucleophilicity of O-2 oxygen was reduced by incorporation of an adjacent electron withdrawing nitro substituent at N-3. The introduction of the 3-N-nitro group proceeded rapidly (nitronium trifluoroacetate, 1 min) and in quantitative yield. A one-pot method to remove the 3-N-nitro group by reductive nitration (zinc metal in acetic acid, 5 min) and the silyl protecting groups of the alkyne and 3′,5′ hydroxyls (fluoride reagent, 16 h) was established as the final synthetic step. This application of the 3-N-nitro protecting group addresses the significant shortfalls of the conventional approach to synthesis of 2′ modified nucleosides, wherein condensation of a 2′ modified sugar fragment with a pyrimidine base provides poor stereocontrol of N-glycosylation, low yields and incompatibility with 2′ iodo sugars.
A solid-supported acidic oxazolium perchlorate as an easy-handling catalyst for the synthesis of modified pyrimidine nucleosides via Vorbrüggen-type N-glycosylation
Basu, Nabamita,Oyama, Kin-ichi,Tsukamoto, Masaki
supporting information, p. 1921 - 1924 (2017/04/27)
A solid-supported acidic oxazolium perchlorate was investigated as a heterogeneous catalyst in N-glycosylation reactions using silylated modified pyrimidines and an acylated ribose or glucose to afford the corresponding pyrimidine nucleosides. This salt is a nonhygroscopic and stable powder whose activity is comparable to that of 2-methyl-5-phenylbenzoxazolium perchlorate. A reaction with this polymer catalyst can be conducted on a gram scale. Reusability of the solid-supported catalyst was also investigated.
Synthesis of 4-thio-5-(2′′-thienyl)uridine and cytotoxicity activity against colon cancer cells: In vitro
Zhang, Xiaohui,Li, Depeng,Qin, Jianzhong,Xu, Yaozhong,Ma, Kedong
, p. 70099 - 70105 (2016/08/05)
A novel anti-tumor agent 4-thio-5-(2′′-thienyl)uridine (6) was synthesized and the in vitro cytotoxicity activity against mice colon cancer cells (MC-38) and human colon cancer cells (HT-29) was evaluated by MTT assay. The results showed that the novel compound had antiproliferative activity toward MC-38 and HT-29 cells in a dose-dependent manner. The cell cycle analysis by flow cytometry indicated that compound 6 exerted in tumor cell proliferation inhibition by arresting HT-29 cells in the G2/M phase. In addition, cell death detected by propidium iodide staining showed that compound 6 efficiently induced cell apoptosis in a concentration-dependent manner. Moreover, the sensitivity of human fibroblast cells to compound 6 was far lower than that of tumor cells, suggesting the specific anti-tumor effect of 4-thio-5-(2′′-thienyl)uridine. Taken together, novel compound 6 effectively inhibits colon cancer cell proliferation, and hence would have potential value in clinical application as an antitumor agent.
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
Fluorescent nucleoside derivatives as a tool for the detection of concentrative nucleoside transporter activity using confocal microscopy and flow cytometry
Claudio-Montero, Ana,Pinilla-Macua, Itziar,Fernández-Calotti, Paula,Sancho-Mateo, Carlos,Lostao, Mar?a Pilar,Colomer, Dolors,Grandas, Anna,Pastor-Anglada, Mar?al
, p. 2158 - 2166 (2015/06/16)
The abundance and function of transporter proteins at the plasma membrane are likely to be crucial in drug responsiveness. Functional detection of human concentrative nucleoside transporters (hCNTs) is of interest for predicting drug sensitivity because of their ability to transport most nucleoside-derived drugs. In the present study, two fluorescent nucleoside analogues, uridine-furan and etheno-cytidine, were evaluated as tools to study in vivo nucleoside transporter-related functions. These two molecules showed high affinity interactions with hCNT1 and hCNT3 and were shown to be substrates of both transporters. Both fluorescence microscopy and flow cytometry experiments showed that uridine-furan uptake was better suited for distinguishing cells that express hCNT1 or hCNT3. These data highlight the usefulness of fluorescent nucleoside derivatives, as long as they fulfill the requirements of confocal microscopy and flow cytometry, for in vivo analysis of hCNT-related function.
NEW PRODUCTION METHOD FOR PYRIMIDINE NUCLEOSIDE DERIVATIVES
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Paragraph 0043; 0061, (2018/10/31)
PROBLEM TO BE SOLVED: To provide a method for producing pyrimidine nucleoside derivatives with excellent handleability. SOLUTION: A glycosyl donor of which OH groups at positions 1 and 2 are acylated and other OH groups are protected and a silylated pyrimidine derivative are reacted in the presence of an acid azole/pyridine conjugate of the following general formula (1) or (2) and a solvent. Acid azole/pyridine conjugate is excellent in handleability because it has no or low hygroscopicity. In the formula (1), A is -O- or -S-, in the formulae (1) and (2), R1-R8 are hydrocarbon groups which may be substituted, R1-R8 may form a ring by binding to other R1-R8, the acid azole/pyridine conjugate may comprise plurality of formula (1) and/or formula (2) as partial structures. Further, it may be bonded to a carrier via R1-R8. COPYRIGHT: (C)2015,JPO&INPIT
Synthesis of modified pyrimidine nucleosides via Vorbrüggen-type N-glycosylation catalyzed by 2-methyl-5-phenylbenzoxazolium perchlorate
Shirouzu, Hiroshi,Morita, Hiroki,Tsukamoto, Masaki
supporting information, p. 3635 - 3639 (2014/05/20)
Several acidic azolium salts prepared from oxazole, thiazole, and imidazole derivatives were investigated as catalysts in N-glycosylation reaction using a silylated modified pyrimidine and an acylated ribose or glucose to afford the corresponding pyrimidine nucleoside. Among the salts, 2-methyl-5- phenylbenzoxazolium perchlorate showed the highest catalytic activity. This salt is a nonhygroscopic crystalline compound that shows higher activity than the frequently used trimethylsilyl triflate. Reactions with this salt can be conducted in gram scales.
