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Nucleosides, Nucleotides & Nucleic Acids

Yamini Thakur, Mamta Tripathi, Bharati Verma, Rubi Khilari, Rainy Agrawal, Likheshwari, Mohammad Khursheed Siddiqi, Rama Pande, Eli Mohapatra, Rizwan Hasan Khan
The polyadenylic acid [poly(A)] tail of mRNA plays a noteworthy role in the initiation of the translation, maturation, and stability of mRNA. It also significantly contributes to the production of alternate proteins in eukaryotic cells. Hence, it has recently been recognized as a prospective drug target. Binding affinity of bis(N-p-tolylbenzohydroxamato)Cobalt(II), [N-p-TBHA-Co(II)] (1) and bis(N-p-naphthylbenzohydroxamato)Copper(II), [N-p-NBHA-Cu(II)] (2) complexes with poly(A) have been investigated by biophysical techniques namely, absorption spectroscopy, fluorescence spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy, circular dichroism spectroscopy, viscometric measurements and through molecular docking studies...
February 7, 2019: Nucleosides, Nucleotides & Nucleic Acids
Galal H Elgemeie, Sheikha A Alkhursani, Reham A Mohamed
Pyrimidinethione nucleosides are effective compounds and have significant and pivotal effects in several fields. New synthetic strategies for many pyrimidinethione nucleosides including acyclic and cyclic derivatives have been reported.
February 7, 2019: Nucleosides, Nucleotides & Nucleic Acids
Ramakrishnamraju Samunuri, Ashok Kumar Jha, Chandralata Bal
The need of long-term treatment for chronic HBV, emergence of drug-resistant viruses and inefficiency of currently approved therapies to eliminate covalently closed circular DNA (cccDNA), mandates identification of potent and selective inhibitors of HBV replication with novel mechanisms of action. Entecavir, a carbocyclic guanosine nucleoside analog, is the most potent inhibitor of HBV replication on the market. Moreover, the naturally occurring carbocyclic nucleosides aristeromycin are known for their wide range of antiviral activities...
January 28, 2019: Nucleosides, Nucleotides & Nucleic Acids
Navaneetha Nambagari, Shyam Perka, Ravi Kumar Vuradi, S Satyanarayana
Three new cobalt(III) polypyridyl complexes, [Co(L - L)2 IIP]3+ where IIP = 2-(2H-isoindol-1-yl)-2H-imidazo[4,5-f][1, 10]phenanthroline, L = 1) phen (1,10-phenanthroline), 2) bpy (2,2'bipyridyl), 3) dmb (4, 4-dimethyl 2, 2'-bipyridine) have been synthesized, characterized (UV -VIS, IR, 1 HNMR and 13 C NMR spectroscopy) and screened for their in vitro antibacterial activity against E.coli, Staphylococcus aureus and Bacillus subtilis. The binding of these complexes with calf-thymus DNA (CT-DNA) has been investigated by absorption and fluorescence spectroscopy, viscosity measurements...
January 28, 2019: Nucleosides, Nucleotides & Nucleic Acids
Farhad Ahmadi, Nosaibeh Shabrandi, Leilah Hosseinzadeh, Homa Azizian
A complex of metronidazole (MTZ) with zinc ion was synthesized and characterized by UV-Vis, Fourier transform infrared (FT-IR), 1 H-NMR, X-ray crystallography and thermal gravimetric-differential thermal analysis (TG-DTA). The cytotoxicity effect of the synthesized complex investigated over SKNMC, A549, MCF-7, and MCDK cell lines and the results have shown that it has high cytotoxic potential over cancer cell lines. In order to clarify the mechanism of cell cytotoxicity, the oxidative stress and binding of the complex to the calf thymus-DNA studied by evaluating the intrinsic binding constant and defining thermodynamic parameters of complex over the DNA accompanying with in silico molecular modeling method...
January 28, 2019: Nucleosides, Nucleotides & Nucleic Acids
Mamdouh A Abu-Zaied, Galal H Elgemeie
This study reports a novel method for the synthesis of a new class of pyrazole thioglycosides 7a-h as pyrazomycin analogues. These series of compounds were designed through the reaction of sodium 2-cyano-3-oxo-3-(4-substitutedphenylamino)prop-1-ene-1,1-bis(thiolate) salts 2 with phenyl hydrazine in ethanol at room temperature to give the corresponding sodium 5-amino-4-(substitutedphenylcarbamoyl)-1-phenyl-1H-pyrazole-3-thiolates 3a-d. The latter compounds were treated with tetra-acetylated glycosyl bromides 4a,b in DMF at ambient temperature to give the corresponding pyrazole thioglycosides 6a-h...
January 28, 2019: Nucleosides, Nucleotides & Nucleic Acids
Richard J Honeywell, Dzjemma Sarkisjan, Michael H Kristensen, Daniel J de Klerk, Godefridus J Peters
DNA methylation plays an important role in carcinogenesis and aberrant methylation patterns have been found in many tumors. Methylation is regulated by DNA methyltransferases (DNMT), catalyzing DNA methylation. Therefore inhibition of DNMT is an interesting target for anticancer treatment. RX-3117 (fluorocyclopentenylcytosine) is a novel demethylating antimetabolite that is currently being studied in clinical trials in metastatic bladder and pancreatic cancers. The active nucleotide of RX-3117 is incorporated into DNA leading to downregulation of DNMT1, the maintenance DNA methylation enzyme...
January 19, 2019: Nucleosides, Nucleotides & Nucleic Acids
Iwona Pelikant-Małecka, Ryszard T Smoleński, Ewa M Słomińska
4-pyridone-3-carboxamide-1β-D-ribonucleoside (4PYR) is a derivative of nicotinamide found physiologically in human body fluids that can be metabolized to mono-, di- or triphosphate derivatives (4PYMP, 4PYDP and 4PYTP respectively) and an analogue of NAD - the 1-β-D-ribonucleoside-4-pyridone-3-carboxamide adenine dinucleotide (4PYRAD) in human cells. The European Uremic Toxin Work Group (EUTox) has classified 4PYR as a uremic toxin that adversely affects endothelium. This study aimed to investigate the metabolism of 4PYR in murine brain microvascular endothelial cells (mBMECs)...
January 19, 2019: Nucleosides, Nucleotides & Nucleic Acids
Paulina Mierzejewska, Teresa Gawlik-Jakubczak, Patrycja Jablonska, Mateusz Czajkowski, Barbara Kutryb-Zajac, R T Smolenski, Marcin Matuszewski, Ewa M Slominska
OBJECTIVES: Cancer is one of the main cause of death in Western countries. Inflammation plays an important role in the pathogenesis of cancer. Nicotinamide (NA) - known for its anti-inflammatory properties - participates in the processes related to the cell cycle regulation and DNA repair, which are relevant in cancer development. This study aimed to investigate the nicotinamide metabolism alterations in bladder cancer. METHODS: Blood and plasma samples of patients with bladder cancer were collected...
January 19, 2019: Nucleosides, Nucleotides & Nucleic Acids
Yusuke Maeda, Rintaro Iwata Hara, Kazutaka Nishina, Kie Yoshida-Tanaka, Taiichi Sakamoto, Takanori Yokota, Takeshi Wada
Properties of cationic peptides bearing amino or guanidino groups with various side chain lengths that bind to double stranded RNAs (dsRNAs) were investigated. Peptides with shorter side chain lengths effectively bound to dsRNAs (12mers) increasing their thermal stability. NMR measurements suggested that the cationic peptide binds to the inner side of the major groove of dsRNA. These peptides also increased the thermal stability of siRNA and effectively protected from RNase A digestion. On the other hand, both peptides containing amino groups and guanidine groups did not disturb RNAi activity...
January 19, 2019: Nucleosides, Nucleotides & Nucleic Acids
Godefridus J Peters
DUP-785 (Brequinar sodium) is a potent inhibitor of the mitochondrial dihydroorotate dehydrogenase (DHO-DH), a rate-limiting enzyme in the pyrimidine de novo nucleotide synthesis. In phase I clinical studies at the maximum tolerated dose (MTD) Brequinar induced a long-term inhibition of DHO-DH in white blood cells (WBC) and a long-term depletion of plasma uridine. These two parameters were related to severe myelosuppression, so that in Phase II studies the dose of Brequinar was decreased considerably. We further characterized the mechanism of DHO-DH enzyme inhibition while in blood samples of patients entered into Phase II studies we evaluated DHO-DH inhibition in WBC and plasma uridine depletion...
January 19, 2019: Nucleosides, Nucleotides & Nucleic Acids
Hany A Eldeab
An efficient, mild and rapid procedure was employed to prepare a novel series of pyridine glycosides. The protocol allows the reaction of 2-pyridone with 1,2,3,4,6-penta-O-acetyl-α-D-glucopyranose under solvent-free microwave-assisted synthesis using different solid supports. Silica gel has been found to be an efficient and environmentally friendly promoter. Structures of the new products were confirmed based on their elemental analyses and spectral data (LC-MS/MS, IR, UV, 1D- and 2D-NMR).
January 19, 2019: Nucleosides, Nucleotides & Nucleic Acids
Marta Tomczyk, Paulina Mierzejewska, Ewa M Slominska, Ryszard T Smolenski
CD73 inhibitors are considered to be used in the therapies of melanomas, gliomas or breast cancer. However, little is known about their pharmacology and kinetics in mouse experimental models. Thus, this study is aimed to define a metabolic stability and elimination of the adenosine diphosphate (ADP) analog - α,β-Methylene-ADP also known as AOPCP in BALB/c mice. The process starts with an intravenous injection of AOPCP, next blood and serum samples are collected. Urine samples are possessed by a bladder puncture...
January 9, 2019: Nucleosides, Nucleotides & Nucleic Acids
S Karthik, P K Mandal, A Thirugnanasambandam, N Gautham
The X-ray crystal structures of a decamer sequence d(CGCGTACGCG)2 and a tetradecamer sequence d(CGCGCGTACGCGCG)2 are presented here. Both sequences are alternating pyrimidine-purine repeat sequences and they form disordered, pseudo-continuous left handed Z-type helices. They demonstrate interesting variants of the 'bundles of columns of helices' mode of packing.
December 27, 2018: Nucleosides, Nucleotides & Nucleic Acids
Xuan-Ming Zhang, Li-Wen Han, Shan-Shan Zhang, Xiao-Bin Li, Qiu-Xia He, Jian Han, Xi-Min Wang, Ke-Chun Liu
In this study, we investigated the metabonomic profiles of Apostichopus japonicus using an LC-MS-based method in conjunction with multivariate data analysis. Based on the PLS-DA model, 85 differential metabolites (VIP value >1.0) were obtained from viscera and body wall samples. The MS/MS and NMR experiments were used for the qualitative identification of the characteristic peaks. Sphingoid-based nucleoside analogues were the main components in Chinese A. japonicus viscera. Our findings demonstrate that A...
December 27, 2018: Nucleosides, Nucleotides & Nucleic Acids
Lucyna Michalska, Dariusz Wawrzyniak, Agnieszka Szymańska-Michalak, Jan Barciszewski, Jerzy Boryski, Dagmara Baraniak
We describe a simple method for the synthesis of modified dinucleosides containing pyrimidine nucleoside analogues (2'-deoxyuridine, thymidine and 5-fluoro-2'-deoxyuridine). Six different dimers with a 1,2,3-triazole linkage were obtained by azide-alkyne 1,3-dipolar cycloaddition (click reaction), starting from propargylated 2'-deoxyuridine and 5'-azido-nucleoside derivatives. Their cytotoxic activity was tested in five human cancer cell lines: cervical (HeLa), high grade gliomas (U-118 MG, U-87 MG, T98G), liver (HepG2), and normal human fibroblast cell line (MRC-5) using the sulforhodamine B (SRB) assay...
December 27, 2018: Nucleosides, Nucleotides & Nucleic Acids
David Perrett
This paper is a personal review of the role developments in separation science over the last four decades have played in the diagnosis and understanding of purine and pyridine metabolism particularly in man. In 1967 the separation of nucleotides was used to demonstrate a new chromatography technique. This technique became known as HPLC and which continues to dominate the analysis of purines etc. The resolution and quantitation offered by even the earliest HPLC systems completely changed our understanding of matters such as nucleotide instability in cells and tissues, diagnosis of in born errors, etc...
December 27, 2018: Nucleosides, Nucleotides & Nucleic Acids
Kiyoko Kaneko, Mizuho Kabeya, Hirokazu Kondo, Tomoko Fukuuchi, Noriko Yamaoka, Makoto Yasuda, Satoshi Yamaguchi
We examined the mechanism of urinary stone formation by analyzing the matrix proteins in a urinary stone with two layers composed of different crystals. Micro-area X-ray spectrometry and infrared spectroscopy revealed calcium oxalate monohydrate in the outside and uric acid in the inside. We also examined the interface. After the outside, inside, and interface parts were separated, proteomic analysis identified 48, 7, and 4 matrix proteins, respectively. Urinary stones with two layers are considered to have grown under different conditions...
December 27, 2018: Nucleosides, Nucleotides & Nucleic Acids
Barbara Kutryb-Zajac, Alicja Bulinska, Magdalena A Zabielska, Paulina Mierzejewska, Ewa M Slominska, Ryszard T Smolenski
Animal models are widely used in atherosclerosis research. The most useful, economic and valid is mouse genetic model of this pathology. Purinergic signaling is an important mechanism regulating processes involved in the vascular inflammation and atherosclerosis. The aim of this study was to measure vascular activities of nucleotide and adenosine-degrading ecto-enzymes in different strains of mice and to compare them to atherosclerotic susceptibility. The vascular extracellular nucleotide catabolism pathway was analyzed in 6-month-old male genetically unmodified mouse strains: FVB/NJ, DBA/2J, BALB/c, C57Bl/6J and mouse knock-outs on C57Bl/6J background for LDLR (LDLR-/-) and for ApoE and LDLR (ApoE-/-LDLR-/-)...
December 27, 2018: Nucleosides, Nucleotides & Nucleic Acids
Hedieh Sattarifard, Mohammad Hashemi, Shekoufeh Hassanzarei, Abbas Basiri, Behzad Narouie, Saeid Ghavami
The current study aimed to examine the impact of POLR2E rs1046040 and rs3787016 polymorphisms on prostate cancer (PCa) risk in a sample of southeast Iranian population. The present case-control study was performed on 178 patients with PCa and 180 benign prostatic hyperplasia (BPH). Genotyping of the variants was done by mismatch PCR-RFLP. The findings showed that the rs3787016 C > T variant significantly increased the risk of PCa in codominant (OR = 1.84, 95% CI = 1.12-3.03, P = 0.018, CT vs CC), dominant (OR = 1...
December 27, 2018: Nucleosides, Nucleotides & Nucleic Acids
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