共查询到20条相似文献,搜索用时 31 毫秒
1.
《Nucleosides, nucleotides & nucleic acids》2013,32(12):2161-2170
Abstract 1-O-Acetyl-2-deoxy-3,5-di-O-toluoyl-4-thio-D-erythro-pentofuranose and 2-deoxy-1,3,5-tri-O-acetyl-4-thio-L-threo-pentofuranose were coupled with 5-azacytosine to obtain α and β anomers of nucleosides. All four nucleosides were reduced to the corresponding dihydro derivatives and deblocked to give target compounds. All eight target compounds were evaluated in a series of human cancer cell lines in culture. Only 2′-deoxy-4′-thio-5-azacytidine (3β) was found to be cytotoxic in all the cell lines and was further evaluated in vivo. Details of the synthesis and biological activity are reported. 相似文献
2.
Loredana Cappellacci Kamal N. Tiwari John A. Montgomery John A. Secrist III 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):613-614
Abstract 1-O-Acetyl-2-deoxy-3,5-di-O-toluoyl-4-thio-d-erythro-pentofuranose and 2-deoxy-1,3,5-tri-O-acetyl-4-thio-l-threo-pentofuranose were coupled with 5-azacytosine to obtain α and β anomers of nucleosides. 相似文献
3.
《Bioorganic & medicinal chemistry》2014,22(10):2896-2906
Even number fatty acid residues—docosanoyl (behenoyl) and stearoyl were selected for introduction to the N4-position of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine) (HPMPC, cidofovir), and its 5-azacytosine counterpart, (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine) (HPMP-5-azaC) with the aim to prepare a new type of lipophilic prodrugs. The study on the influence of these modifications to the stability and biological activity of both antivirals was performed. Different reactivity of both systems towards acylation reactions was also found: the 4-NH2 group of cidofovir was more reactive compared to that of HPMP-5-azaC. In 5-azacytosine derivatives, we found mostly a destabilizing effect of the N4-acylation but this could be compensated by a positive influence of the esterification of the phosphonate group. Chemical stability of the 5-azacytosine moiety in the HPMP series is increasing in the following order: HPMP-5-azaC < cyclic HPMP-5-azaC < HPMP-5-azaC esters. From the view of prodrug development, the best chemical stability was observed in case of the double prodrug 7: the N4-behenoyl derivative of the hexadecyloxyethyl ester of cyclic HPMP-5-azaC. The free phosphonic acid (N4-behenoyl-HPMPC) appeared to be a more potent and selective inhibitor of herpesvirus replication than the parent HPMPC derivative. 相似文献
4.
Mao-Chin Liu Mei-Zhen Luo Diane E. Mozdziesz Tai-Shun Lin Ginger E. Dutschman Elizabeth A. Gullen 《Nucleosides, nucleotides & nucleic acids》2013,32(3):603-618
Abstract (2R,5S)-5-Amino-2-[2-(hydroxymethyl)-1,3-oxathiolan-5-y1]-1,2,4-triazine-3(2H)-one (8) and (2R,5R)-5-amino-2-[2-(hydroxymethyl)-1,3-oxathiolan-5-y1]-1,2,4-triazine-3(2H)-one (9) have been synthesized via a multi-step procedure from 6-azauridine. (2R,5S)-4-Amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-y1]-1,3,5-triazine-2(1H)-one (11) and (2R,5R)-4-amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-y1]-1,3,5-triazine-2(1H)-one (12), and the fluorosubstituted 3-deazanucleosides (19–24) have been synthesized by the transglycosylation of (2R,5S)-1-{2-[[(tert-butyldiphenylsilyl) oxy]methyl]-1,3-oxathiolan-5-y1} cytosine (2) with silylated 5-azacytosine and the corresponding silylated fluorosubstituted 3-deazacytosines, respectively, in the presence of trimethylsilyl trifluoromethanesulfonate as the catalyst in anhydrous dichloroethane, followed by deprotection of the blocking groups. These compounds were tested in vitro for cytotoxicity against L1210, B16F10, and CCRF-CEM tumor cell lines and for antiviral activity against HIV-1 and HBV. 相似文献
5.
5-Azacytidine 5′-monophosphate (5-aza-CMP) was synthesized enzymatically from 5-azacytidine (5-aza-C) in a reaction catalyzed by uridine-cytidine kinase. In a second step, 5-azacytidine 5′-triphosphate (5-aza-CTP) was synthesized enzymatically from 5-aza-CMP using CMP kinase and nucleoside diphosphokinase. Due to the chemical instability of the triazide ring of 5-azacytosine at neutral and alkaline pH, the enzymatic synthesis and purification of the nucleotides by ion exchange chromatography were performed at acid pH. The enzymatically synthesized 5-aza-CTP had an ultraviolet absorbance spectrum at pH 5.5 similar to the spectrum of 5-aza-C. In the DNA-dependent RNA polymerase reaction, 5-aza-CTP inhibited the incorporation of [3H]CTP, but [3H]UTP, into RNA. 相似文献
6.
Güimil García R Brank AS Christman JK Marquez VE Eritja R 《Antisense & nucleic acid drug development》2001,11(6):369-378
The incorporation of 5-azacytosine residues into DNA causes potent inhibition of DNA (Cytosine-C5) methyltransferases. The synthesis of oligodeoxyribonucleotides incorporating single or multiple 5-aza-2'-deoxycytidine residues at precise sites was undertaken to generate an array of sequences containing the reactive 5-azacytosine base as specific target sites for enzymatic methylation. Preparation of these modified oligonucleotides requires the use of 2-(p-nitrophenyl)ethyloxycarbonyl (NPEOC) groups for the protection of exocyclic amino functions. These groups are removed under mild conditions, thus avoiding conventional protocols that are detrimental to the integrity of the 5-azacytosine ring. 相似文献
7.
Manfred Klaas Manorama C. John Dring N. Crowell Richard M. Amasino 《Plant molecular biology》1989,12(4):413-423
We have optimized conditions for demethylation of the genome and induction of a silent, hypermethylated T-DNA gene (ipt) by 5-azacytosine (5-azaCyt) derivatives in a suspension culture of tobacco cells. In this system, 5-azacytidine (5-azaC) is more effective in causing genomic demethylation and ipt gene induction than 5-azaCyt or 5-azadeoxycytidine (5-azadC). A single treatment with 2.5 M 5-azaC resulted in a maximal level of ipt gene induction without inhibiting cell growth. However, we could not reduce the level of genomic methylation below approximately 2/3 of that found in untreated controls, even after extensive 5-azaC treatment. Furthermore, remethylation of the genome occurred after removal of 5-azaC. The use of 5-azaC as an inducer of silent plant genes is discussed, along with differences in the response of plant and animal genomes to demethylating agents.Abbreviations C
cytidine
- Cyt
cytosine
- 5-azaCyt
5-azacytosine
- 5-azaC
5-azacytidine
- 5-azadC
5-azadeoxycytidine
- m5Cyt
5-methylcytosine 相似文献
8.
Naoya Otomo Hiroji Sato Sadao Sakamura 《Bioscience, biotechnology, and biochemistry》2013,77(3):861-863
Theaspirane has been found as a naturally occurring substance in raspberry, yellow passion fruit and tea.1) The synthesis of theaspirane has been reported by some investigators.2) We now report a new synthesis of theaspirane from β-ionone through dihydro-β-ionol.When two equivalents of aluminium chloride hexahyd-rate (A1C13-6H20) is present in sodium-ammonia reduction, β-ionone (1) can be efficiently reduced to dihydro-β-iaonol (2). The bromination of 2 using cupric bromide, followed by dehydrobromination in the presence of calcium carbonate, affords a mixture of (E)-theaspirane and (Z)-theaspirane. The process of synthesis is outlined in Scheme 1. 相似文献
9.
Marcela Krečmerová Milena Masojídková Antonín Holý 《Bioorganic & medicinal chemistry》2010,18(1):387-395
Two methods for preparation of 6-substituted derivatives of anti DNA-viral agent 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (HPMP-5-azaC) were developed: (1) ammonia mediated ring-opening reaction of diisopropyl esters of HPMP-5-azaC (4) to carbamoylguanidine derivatives followed by ring-closure reaction with orthoesters and (2) condensation reaction of 6-substituted 5-azacytosines with diisopropyl (1S)-[2-hydroxy-1-tosyloxymethyl)ethoxy]methylphosphonate (15). Deprotection of diisopropyl esters to free phosphonic acids was performed with bromotrimethylsilane in acetonitrile followed by hydrolysis. In contrast to parent compound HPMP-5-azaC, a substantial decrease of antiviral activity in case of 6-substituted analogues occurred. Surprisingly, N-3 isomer of 6-methyl-HPMP-5-azaC in the form of isopropyl ester revealed activity against RNA viruses (Sindbis virus). 相似文献
10.
Tai-Shun Lin Xin Guo Mei-Zhen Luo Mao-Chin Liu Yong-Lian Zhu Ginger E. Dutschman 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):619-625
Abstract The pharmacokinetics and toxicology of 2′,3′-dideoxy-β-L-5-fluorocytidine (β-L-FddC) and 2′,3′-dideoxy-β-L-cytidine (β-L-ddC) in mice was investigated. In addition, 2′,3′-dideoxy-β-L-5-azacytidine (β-L-5-aza-ddC) and its α-L-anomer (α-L-5-aza-ddC) were synthesized by coupling the silylated 5-azacytosine derivative with 1-O-acetyl-5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose, followed by separation of the α-and β-anomers and were evaluated in vitro against HBV and HIV. β-L-5-aza-ddC was found to show significant anti-HBV activity at approximately the same level as 2′,3′-dideoxy-β-D-cytidine (ddC), which is a known anti-HBV agent. β-L-5-aza-ddC was not cytotoxic to L1210, P388, S-180, and CCRF-CEM cells up to a concentration of 100 μ. Conversely, the α-L-anomer was not active against HBV at the same concentration. 相似文献
11.
Duplex heavy-light (HL) DNAs synthesized in the presence of brdUrd and methylation inhibitors were separated from bulk cellular DNA by CsCl density gradient centrifugation and analysed for 5-methylcytosine (5mC) contents by HPLC. DNAs synthesized in the presence of 5 mM ethionine or 2 mg/ml cycloleucine were not detectably hypomethylated, was undermethylated with respect to control DNA. The heavy, or H-strand, in which up to 5% of the cytosine residues were replaced by intact 5-azacytosine, was undermethylated and the HL duplex DNA was therefore strand asymmetrically methylated. This duplex DNA served as an efficient substrate for a crude DNA methyltransferase preparation which transferred the methyl group from S-adenosylmethionine specifically into cytosine residues within the hypomethylated H strand. Increasing levels of incorporated 5-azacytosine inhibited the action of the methyltransferase suggesting that incorporation of 5-azacytosine into DNA may be responsible for the inhibitory effect of 5-azacytidine on DNA methylation. 相似文献
12.
Luo MZ Liu MC Mozdziesz DE Lin TS Dutschman GE Gullen EA Cheng YC Sartorelli AC 《Bioorganic & medicinal chemistry letters》2000,10(18):2145-2148
Novel L- and D-configuration dioxolane 5-azacytosine and 6-azathymine nucleosides have been synthesized and evaluated for biological activity. (-)-(2S,4S)-1-[2-(Hydroxymethyl)-1,3-dioxolan-4-yl]-5-azacytosine (6) showed significant activity against HBV, whereas the D-configuration analogue (14) has been found to exhibit potent anti-HIV activity. 相似文献
13.
Hydrolytic decomposition of four 5-azacytosine acyclic nucleoside phosphonates was studied. Products of the decomposition are carbamoylguanidine derivatives. Stability and decomposition products of HPMP-5-azaC (a 5-azacytosine derivative with strong antiviral activity) differ from the other derivatives. The reaction pathway of HPMP-5-azaC involves a formyl derivative formed by intramolecular transformylation reaction. 相似文献
14.
Kantevari S Patpi SR Sridhar B Yogeeswari P Sriram D 《Bioorganic & medicinal chemistry letters》2011,21(4):1214-1217
A series of novel aryl and thiophenyl tethered dihydro-6H-quinolin-5-ones have been synthesized in very good yields through CeCl3·7H2O-NaI catalyzed one-pot condensation of β-enaminones derived from the respective methyl ketones; 1,3-cyclohexanedione & 5,5-dimethyl-1,3-cyclohexanedione and ammonium acetate refluxing in 2-propanol. Dihydro-6H-quinolin-5-ones 3a-f was further derivatized to the respective hydroxymethyl analogs using proline as an organocatalyst in aqueous media. Among the all 18 compounds screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB), dihydro-6H-quinolin-5-ones 4e and 4f were found to be most active with MIC 3.13 μg/mL. 相似文献
15.
Aruna V. Arakali † J. McCloskeyt R. Parthasarathy J. L. Alderfer G. B. Chheda∗∗ T. Srikrishnan 《Nucleosides, nucleotides & nucleic acids》2013,32(12):2193-2218
Abstract Creatinine (2-amino-1,5- dihydro-1-methyl-4-imidazolone) is a natural by-product of cellular metabolism related to muscular mass. It is excreted in human urine and is necessary for normal kidney function. Urinary secretion of creatinine serves as a bench mark for several clinical measurements. Recently, in our laboratories, during the course of an investigation of the urine of cancer patients for tumor markers, we found some new metabolites of creatinine. These were identified as 5-methoxy and 5-ethoxy creatinine by UV, NMR and Mass spectrometry and their tautomeric structures confirmed by crystal structural investigations of the metabolites. The x-ray crystallographic analysis confirmed the structures of the compound and showed that it exists in the 2-amino form. The spectral characteristics of these new compounds and the generality of the reaction are discussed in this paper. Creatinine, when allowed to react with methanol, ethanol and propanol respectively, in the presence of charcoal and air gave the 5-methoxy, 5-ethoxy and 5-propoxy creatinine derivatives respectively, suggesting a generality of a reaction. The reaction of creatinine with alcohols in the presence of charcoal and air takes place through a free radical reaction mechanism. 相似文献
16.
The exposure of freshly isolated, activity growing Ehrlich ascites tumor cells to the antileukemic agent 5-azacytidine and its analogs, 5-azacytosine (but not 6-azacytosine), 5-aza-2'-deoxycytidine and, in particular, 5-fluorocytidine in the serum-free medium caused a time- and dose-dependent suppression of the nuclear ADP-ribosyltransferase activity. The azacytidine suppression was apparently dependent on the cellular activity of DNA synthesis but not related to the nuclear activity of DNA methylation, indicating the 5-azacytidine incorporation into DNA, but not drug-induced hypomethylation of DNA, being responsible for the 5-azacytidine-suppression of chromatin-bound ADP-ribosyltransferase. 相似文献
17.
The normal and vacuum uv spectra of cytosine, 5-azacytosine, and 6-azacytosine thin layers were determined. The spectra were resolved into a series of Gaussian bands and the experimental band positions and oscillator strengths were compared with the calculated values. The calculations were carried out with the PPP-SCF-CI method. The agreement of the calculations with those of others and with the experiment is discussed. 相似文献
18.
Y Deguchi S Negoro H Hara S Kishimoto 《Biochemical and biophysical research communications》1988,151(3):1395-1401
Previous work from our laboratory demonstrated the mitogenic response of human peripheral blood T lymphocytes by phytohemagglutinin (PHA), phorbol myristate acetate (PMA) and ionomycin, or interleukin 2 (IL-2). Increasing levels of incorporated 5-azacytosine inhibited the action of the methyltransferase suggesting that incorporation of 5-azacytosine into DNA could be responsible for the inhibiting effect of 5-azacytidine (5-aza-CR) on DNA methylation. In this study, we first demonstrated the inhibition of mitogenic response by agents, such as PHA, PMA and ionomycin, or IL-2, that activate or augment activation of human peripheral blood T cells by treatment of the analog 5-azacytidine. Over 1 microM of 5-azacytidine, we detected significant inhibition of proliferative response and over 5 microM of 5-azacytidine toxic effect of cell viability. We found no significant change of T cell subsets after treatment of 5-azacytidine. 相似文献
19.
《Bioscience, biotechnology, and biochemistry》2013,77(10):1643-1645
The syntheses and biological activities of dihydro-5,6-dehydrokawain derivatives against plant pathogenic fungi and termites were investigated. Dihydro-5,6-dehydrokawain was isolated by a simple method without chromatography from the leaves of Alpinia speciosa K. Schum. The white crystalline compound obtained was identified as dihydro-5,6-dehydrokawain (1) by instrumental analyses. 4-Hydroxy-6-(2-phenylethyl)-2H-pyran-2-one (3) was prepared by hydrolyzing dihydro-5,6-dehydrokawain. Three dihydro-5,6-dehydrokawain derivatives were synthesized by reacting 3 with phosphoric agents.Among the synthesized compounds, dimethyl [6-(2-phenylethyl)-2-oxo-2H-pyran-4-yl] phosphorothionate (4) had the strongest antifungal activity of 91% at 100 ppm against Corticium rolfsii. 相似文献
20.
Kosaku Hirota Tetsuo Tomishi Yoshifumi Maki Hironao Sajiki 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):161-173
Abstract Novel synthetic method of 5-arylthiouridine derivatives is described. Treatment of 5-bromo-2′,3′-O-isopropylideneuridine (1a) with diaryl disulfides in the presence of sodium hydride at ambient temperature gave the 5-arylthiouridines (2) in moderate yields. The present method is devised by virtue of a combination of efficient participation of the 5′-hydroxy group onto the uracil ring and the electrophilic nature of diaryl disulfide, which was applied to the synthesis of 5-arylthio-1-β-D-arabinofuranosyl-uracils (8). 相似文献