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91.
《Nucleosides, nucleotides & nucleic acids》2013,32(8-9):1499-1502
In the present study, we investigated the effect of fluoropyrimidines on the growth of Ureaplasma urealyticum. Addition of fluoropyrimidines strongly inhibited bacterial growth. Growth inhibition by these analogues could be reversed by addition of either thymidine or deoxyuridine, suggesting inhibition of thymidylate biosynthesis as the mechanism in operation. 相似文献
92.
Jeffery C. Hanvey Elma Smal Robert J. Suhadolnik David C. Baker 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):495-496
Abstract Studies on t h e biosynthesis o f the N-nucleoside antibiotics have established that the purine and pyrimidine nucleosides/nucleotides serve as the carbon and nitrogen skeleton, whereas with the C-nucleoside antibioticus, the C-N precursor forthe aglycon is either acetate or glutamate. With the pyrrolopyrimidine nucleoside antibiotics (toyocamycin, tubercidin, and sangi vamycin), either two or three carbons of the N-riboside/ribotide of GTP contribute to carbons 5 and 6 of the pyrrolering and the cyano or carboxamide group. With the naturally occurring nucleoside antibiotic containing the 1,3-diazepine seven-membered ring,2′-deoxycoformycin (dCF)(I), the precursor is not immediately obvious. 相似文献
93.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-7):305-318
1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine) is structurally 4-deamino cytidine. The increased electrophilic character of this simple aglycon endows the molecule with unique chemical and biological properties, making zebularine a versatile starting material for the synthesis of complex nucleosides and an effective inhibitor of cytidine deaminase and DNA cytosine methyltransferase. Zebularine is a stable, antitumor agent that preferentially targets cancer cells and shows activity both in vitro and in experimental animals, even after oral administration. 相似文献
94.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):1339-1342
Abstract Interesting and very promising antisense properties of 2′-deoxy-2′-fluoroarabinonucleic acids ((a) Wilds, C.J.; Damha, M.J. 2′-Deoxy-2′-fluoroarabinonucleosides and oligonucleotides (2′F-ANA): synthesis and physicochemical studies. Nucl. Acids Res. 2000, 28, 3625–3635; (b) Viazovkina, E.; Mangos, M.; Elzagheid, M.I.; Damha, M.J. Current Protocols in Nucleic Acid Chemistry 2002, 4.15.1–4.15.21) (2′F-ANA) has encouraged our research group to optimize the synthetic procedures for 2′-deoxy-2′-fluoro-β-D-arabinonucleosides (araF-N). The synthesis of araF-U, araF-T, araF-A and araF-C is straightforward, (Tann, C.H.; Brodfuehrer, P.R.; Brundidge, S.P.; Sapino, C., Jr. Howell H.G. Fluorocarbohydrates in synthesis. An efficient synthesis of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodouracil (β-FIAU) and 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)thymine (β-FMAU). J. Org. Chem. 1985, 50, 3644–3647; Howell, H.G.; Brodfuehrer, P.R.; Brundidge, S.P.; Benigni, D.A.; Sapino, C., Jr. Antiviral nucleosides. A stereospecific, total synthesis of 2′-fluoro-2′-deoxy-β-D-arabinofuranosyl nucleosides. J. Org. Chem. 1988, 53, 85–88; Maruyama, T.; Takamatsu, S.; Kozai, S.; Satoh, Y.; Izana, K. Synthesis of 9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine bearing a selectively removable protecting group. Chem. Pharm. Bull. 1999, 47, 966–970) however, the synthesis of the guanine analogue is more complicated and affords poor to moderate yields of araF-G (4) ((a) Elzagheid, M.I.; Viazovkina, E.; Masad, M.J. Synthesis of protected 2′-deoxy-2′-fluoro-β-D-arabinonucleosides. Synthesis of 2′-fluoroarabino nucleoside phosphoramidites and their use in the synthesis of 2′F-ANA. Current Protocols in Nucleic Acid Chemistry 2002, 1.7.1–1.7.19; (b) Tennila, T.; Azhayeva, E.; Vepsalainen, J.; Laatikainen, R.; Azhayev, A.; Mikhailopulo, I. Oligonucleotides containing 9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-adenine and -guanine: synthesis, hybridization and antisense properties. Nucleosides, Nucleotides and Nucl. Acids 2000, 19, 1861–1884). Here we describe an efficient synthesis of araF-G (4) that involves coupling of 2-deoxy-2-fluoro-3,5-di-O-benzoyl-α-D- arabinofuranosyl bromide (1) with 2-chlorohypoxanthine (2) to afford 2-chloro-β-araF-I (3) in 52% yield. Nucleoside (3) was transformed into araF-G (4) by treatment with methanolic ammonia (150°C, 6 h) in 67% yield. 相似文献
95.
Vijaya L. Damaraju Delores Mowles Sylvia Yao Amy Ng James D. Young Carol E. Cass 《Nucleosides, nucleotides & nucleic acids》2013,32(3):236-255
The nucleoside analogs 5-azacytidine (azacitidine) and 5-aza-2′-deoxycytidine (decitabine) are active against acute myeloid leukemia and myelodysplastic syndromes. Cellular transport across membranes is crucial for uptake of these highly polar hydrophilic molecules. We assessed the ability of azacitidine, decitabine, and, for comparison, gemcitabine, to interact with human nucleoside transporters (hNTs) in Saccharomyces cerevisiae cells (hENT1/2, hCNT1/2/3) or Xenopus laevis oocytes (hENT3/4). All three drugs inhibited hCNT1/3 potently (K i values, 3–26 μM), hENT1/2 and hCNT2 weakly (K i values, 0.5–3.1 mM), and hENT3/4 poorly if at all. Rates of transport of [3H]gemcitabine, [14C]azacitidine, and [3H]decitabine observed in Xenopus oocytes expressing individual recombinant hNTs differed substantially. Cytotoxicity of azacitidine and decitabine was assessed in hNT-expressing or hNT-deficient cultured human cell lines in the absence or presence of transport inhibitors where available. The rank order of cytotoxic sensitivities (IC 50 values, μM) conferred by hNTs were hCNT1 (0.1) > hENT1 (0.3) ? hCNT2 (8.3), hENT2 (9.0) for azacitidine and hENT1 (0.3) > hCNT1 (0.8) ? hENT2, hCNT2 (>100) for decitabine. Protection against cytotoxicity was observed for both drugs in the presence of inhibitors of nucleoside transport, thus suggesting the importance of hNTs in manifestation of toxicity. In summary, all seven hNTs transported azacitidine, with hCNT3 showing the highest rates, whereas hENT1 and hENT2 showed modest transport and hCNT1 and hCNT3 poor transport of decitabine. Our results show for the first time that azacitidine and decitabine exhibit different human nucleoside transportability profiles and their cytotoxicities are dependent on the presence of hNTs, which could serve as potential biomarkers of clinical response. 相似文献
96.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):623-627
Abstract Preparation of the nucleoside analogues 1 and incorporation of 1, B = T, in deoxyribooligonucleotides by the phosphoramidite method is described. A two-step deprotection procedure was developed to reduce cleavage of the modified allylic unit. The binding properties of the modified oligonucleotides towards complementary DNA and RNA has been evaluated by Tm measurements showing a ΔTm of ?2 to ?6.5°C per modification. An oligonucleotide with two modifications at the 3′-end showed considerable resistance towards cleavage by a 3′-exonuclease. No antiviral activity against HIV-1 or HSV-1 was found for 1, B = G or T, or for any of the trihydroxy derivatives 5. 相似文献
97.
Olga Adelfinskaya Weidong Wu V. Jo Davisson Donald E. Bergstrom 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1919-1945
Two novel C-linked oxadiazole carboxamide nucleosides 5-(2′-deoxy-3′,5′-β-D-erythro-pentofuranosyl)-1,2,4-oxadiazole-5-carboxamide (1) and 5-(2′-deoxy-3′,5′-β-D-erythro-pentofuranosyl)-1,2,4-oxadiazole-3-carboxamide (2) were successfully synthesized and characterized by X-ray crystallography. The crystallographic analysis shows that both unnatural nucleoside analogs 1 and 2 adapt the C2′-endo (“south”) conformation. The orientation of the oxadiazole carboxamide nucleobase moiety was determined as anti (conformer A) and high anti (conformer B) in the case of the nucleoside analog 1 whereas the syn conformation is adapted by the unnatural nucleoside 2. Furthermore, nucleoside analogs 1 and 2 were converted with high efficiency to corresponding nucleoside triphosphates through the combination chemo-enzymatic approach. Oxadiazole carboxamide deoxyribonucleoside analogs represent valuable tools to study DNA polymerase recognition, fidelity of nucleotide incorporation, and extension. 相似文献
98.
Ravi K. Ujjinamatada Yankanagouda S. Agasimundin Peng Zhang Ramachandra S. Hosmane Roman Schuessler Peter Borowski 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1775-1788
The attempted synthesis of a ring-expanded guanosine (1) containing the imidazo[4,5-e][1,3]diazepine ring system by condensation of 1-(2′-deoxy-β-D-erythropentofuranosyl)-4-ethoxycarbonylimidazole-5-carbaldehyde (2) with guanidine resulted in the formation of an unexpected product, 1-(2′-deoxy-β-D-erythropentofuranosyl)-5-(2,4-diamino-3,6-dihydro-1,3,5-triazin-6-yl)imidazole-4-carboxamide (7). The structure as well as the pathway of formation of 7 was corroborated by isolation of the intermediate, followed by its conversion to the product. Nucleoside 7 showed promising in vitro anti-helicase activity against the West Nile virus NTPase/ helicase with an IC 50 of 3-10 μg/mL. 相似文献
99.
Panagiotis Ioannidis Björn Classon Bertil Samuelsson Ingemar Kvarnström 《Nucleosides, nucleotides & nucleic acids》2013,32(5):449-462
Abstract 1-(2,3-Dideoxy-2-C-hydroxymethyl-β-D-threo-pentofuranosyl)-, 1-(2,3-didehydro-2,3-dideoxy-2-C-hydroxymethyl-β-D-glycero-pentofuranosyl)- and 1-(2-C-azidomethyl-2,3-didehydro-2,3-dideoxy-β-D-glycero-pentofuranosyl)uracuracil, thymine and cytosine were synthesized and evaluated for their anti-HIV activities. A key step of the synthesis involves a novel alcohol transposition of2-methylene-nucleoside analogues. 相似文献
100.
Chang Hyun Oh Jin Woo Kim Joon Hee Hong 《Nucleosides, nucleotides & nucleic acids》2013,32(8):871-878
Novel vinyl branched apiosyl nucleosides were synthesized in this study. Apiosyl sugar moiety was constructed by sequential ozonolysis and reductions. The bases (uracil and thymine) were efficiently coupled by glycosyl condensation procedure (persilyated base and TMSOTf). The antiviral activities of the synthesized compounds were evaluated against the HIV-1, HSV-1, HSV-2, and HCMV. Compound 10β displayed moderate anti-HIV activity (EC50 = 17.3 μg/mL) without exhibiting any cytotoxicity up to 100 μM. 相似文献