Design, synthesis, and evaluation of 4'-phosphonomethoxy pyrimidine ribonucleosides as potential anti-influenza agents.

Influenza viruses belong to the Orthomyxoviridae family and cause acute respiratory distress in humans. The developed drug resistance toward existing drugs and the emergence of viral mutants that can escape vaccines mandate the search for novel antiviral drugs. Herein, the synthesis of epimeric 4'-methyl-4'-phosphonomethoxy [4'-C-Me-4'-C-(O-CH P═O)] pyrimidine ribonucleosides, their phosphonothioate [4'-C-Me-4'-C-(O-CH P═S)] derivatives, and their evaluation against an RNA viral panel are described.

Design, Synthesis, Characterization, and Molluscicidal Activity Screening of New Nicotinonitrile Derivatives against Land Snails, .

A new series of nicotinonitrile derivatives - was designed and synthesized from the starting material ()-3-(4-chlorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one () to assess their molluscicidal activity. The newly synthesized nicotinonitrile compounds - were characterized based on FTIR, H-NMR, and C-APT NMR spectra as well as elemental microanalyses. The target compounds - were screened for their toxicity effect against land snails and were compared to Acetamiprid as a reference compound.

Evaluation of Green Silver Nanoparticles Fabricated by Phycocyanin as Anticancer and Antimicrobial Agents.

Green nanotechnology has attracted attention worldwide, especially in treating cancer and drug-resistant section 6 microbes. This work aims to investigate the anticancer activity of green silver nanoparticles synthesized by phycocyanin (SPAgNPs) on two cancer cell lines: Lung cancer cell line (A-549) and breast cancer cell line (MCF-7), compared to the normal human lung cell line (A138). We also aimed to investigate the bactericidal activity against ATCC29737, ATCC11778, ATCC8379, and , as well as the fungicidal activity against (ATCC6019) and .

Quantitative 1HNMR Spectroscopy: Analysis of Zinc Gluconate in Utozinc® Tablets, a Mixture of Zinc Gluconate and Vitamin C.

Background: Zinc is an essential metal for humans and plays key roles in several biological events such as immunity, allergy, growth, and inflammation. The deficiency in zinc causes an increased infection rate with pathogens. Organo-zincates such as zinc gluconate are known for better absorption compared with their inorganic zinc salts.

Probing the Substrate Requirements of the In Vitro Geranylation Activity of Selenouridine Synthase (SelU).

Natural RNA modifications diversify the structures and functions of existing nucleic acid building blocks. Geranyl is one of the most hydrophobic groups recently identified in bacterial tRNAs. Selenouridine synthase (SelU, also called mnmH) is an enzyme with a dual activity which catalyzes selenation and geranylation in tRNAs containing 2-thiouridine using selenophosphate or geranyl-pyrophosphate as cofactors.

Design and Synthesis of Novel 1,3,4-Oxadiazole and 1,2,4-Triazole Derivatives as Cyclooxygenase-2 Inhibitors with Anti-inflammatory and Antioxidant activity in LPS-stimulated RAW264.7 Macrophages.

In an attempt to obtain new candidates with potential anti-inflammatory activity, two series of 1,3,4-oxadiazole based derivatives (8a-g) and 1,2,4-triazole based derivatives (10a,b and 11a-g) were synthesized and evaluated for their COX-1/COX-2 inhibitory activity. In vitro assays showed potent COX-2 inhibitory activity and selectivity of the novel designed compounds (IC = 0.04 - 0.

Fluorescence-Based Binding Characterization of Small Molecule Ligands Targeting CUG RNA Repeats.

Pathogenic CUG and CCUG RNA repeats have been associated with myotonic dystrophy type 1 and 2 (DM1 and DM2), respectively. Identifying small molecules that can bind these RNA repeats is of great significance to develop potential therapeutics to treat these neurodegenerative diseases. Some studies have shown that aminoglycosides and their derivatives could work as potential lead compounds targeting these RNA repeats.

Synthesis of 6-Aza-2-Hydroxyimino-5-Methylpyrimidine Nucleosides for Antiviral Evaluation.

The syntheses of a series of novel 6-aza-2-hydroxyimino-5-methylpyrimidine and related nucleosides are described. A suitably protected 2-methylthiopyrimidine nucleoside was selected as the precursor for installing a hydroxyimino moiety at the C-2 position. The starting nucleobase 6-aza-5-methyl-2-thiouracil is prepared in two steps from thiosemicarbazone and ethyl pyruvate.

Exosomes in Alzheimer's Disease: From Being Pathological Players to Potential Diagnostics and Therapeutics.

Exosomes (EXOs) were given attention as an extracellular vesicle (EV) with a pivotal pathophysiological role in the development of certain neurodegenerative disorders (NDD), such as Parkinson's and Alzheimer's disease (AD). EXOs have shown the potential to carry pathological and therapeutic cargo; thus, researchers have harnessed EXOs in drug delivery applications. EXOs have shown low immunogenicity as natural drug delivery vehicles, thus ensuring efficient drug delivery without causing significant adverse reactions.

Synthesis of 9-(6-Deoxy-α-L-Talofuranosyl)-6-Methylpurine and 9-(6-Deoxy-β-D-Allofuranosyl)-6-Methylpurine Nucleosides.

6-Methylpurine (MeP) is a cytotoxic adenine analog that does not exhibit selectivity when administered systemically and could be very useful in a gene therapy approach to cancer treatment involving Escherichia coli purine nucleoside phosphorylase (PNP). 9-(6-Deoxy-β-D-allofuranosyl)-6-methylpurine [methyl(allo)-MePR, 18] and 9-(6-deoxy-α-L-talofuranosyl)-6-methylpurine [methyl(talo)-MePR, 21] were synthesized as potential prodrugs for MeP in the E. coli PNP/prodrug cancer gene therapy approach.

3-Trifluoromethylpyrazolones derived nucleosides: Synthesis and antiviral evaluation.

Dengue (DENV) viral infection is a global public health problem that infrequently develops life threatening diseases such as dengue hemorrhagic fever (DFS) and dengue shock syndrome (DSS). Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human corona virus with 38% fatality rate of infected patients. A series of 4-arylhydrazono-5-trifluoromethyl-pyrazolones, their ribofuranosyl, and 5'-deoxyribofuranosyl nucleosides were synthesized, geometry optimized using Density functional theory (DFT), and evaluated for their antiviral activity.

Cyano Modification on Uridine Decreases Base-Pairing Stability and Specificity through Neighboring Disruption in RNA Duplex.

5-Cyanomethyluridine (cnm U) and 5-cyanouridine (cn U), the two uridine analogues, were synthesized and incorporated into RNA oligonucleotides. Base-pairing stability and specificity studies in RNA duplexes indicated that cnm U slightly decreased the stability of the duplex but retained the base-pairing preference. In contrast, cn U dramatically decreased both base-pairing stability and specificity between U:A and other noncanonical U:G, U:U, and U:C pairs.

Construction and structure studies of DNA-bipyridine complexes as versatile scaffolds for site-specific incorporation of metal ions into DNA.

The facile construction of metal-DNA complexes using 'Click' reactions is reported here. A series of 2'-propargyl-modified DNA oligonucleotides were initially synthesized as structure scaffolds and were then modified through 'Click' reaction to incorporate a bipyridine ligand equipped with an azido group. These metal chelating ligands can be placed in the DNA context in site-specific fashion to provide versatile templates for binding various metal ions, which are exchangeable using a simple EDTA washing-and-filtration step.

Lithium Hexamethyldisilazane Transformation of Transiently Protected 4-Aza/Benzimidazole Nitriles to Amidines and their Dimethyl Sulfoxide Mediated Imidazole Ring Formation.

Trimethylsilyl-transient protection successfully allowed the use of lithium hexamethyldisilazane to prepare benzimidazole (BI) and 4-azabenzimidazole (azaBI) amidines from nitriles in 58-88% yields. This strategy offers a much better choice to prepare BI/azaBI amidines than the lengthy, low-yielding Pinner reaction. Synthesis of aza/benzimidazole rings from aromatic diamines and aldehydes was affected in dimethyl sulfoxide in 10-15 min, while known procedures require long time and purification.

6-Methylpurine derived sugar modified nucleosides: Synthesis and evaluation of their substrate activity with purine nucleoside phosphorylases.

6-Methylpurine (MeP) is cytotoxic adenine analog that does not exhibit selectivity when administered systemically, and could be very useful in a gene therapy approach to cancer treatment involving Escherichia coli PNP. The prototype MeP releasing prodrug, 9-(β-d-ribofuranosyl)-6-methylpurine, MeP-dR has demonstrated good activity against tumors expressing E. coli PNP, but its antitumor activity is limited due to toxicity resulting from the generation of MeP from gut bacteria.

6-Methylpurine derived sugar modified nucleosides: Synthesis and in vivo antitumor activity in D54 tumor expressing M64V-Escherichia coli purine nucleoside phosphorylase.

Impressive antitumor activity has been observed with fludarabine phosphate against tumors that express Escherichia coli purine nucleoside phosphorylase (PNP) due to the liberation of 2-fluoroadenine in the tumor tissue. 6-Methylpurine (MeP) is another cytotoxic adenine analog that does not exhibit selectivity when administered systemically, and could be very useful in a gene therapy approach to cancer treatment involving E. coli PNP.

Synthesis and antimicrobial evaluation of novel pyrazolones and pyrazolone nucleosides.

The synthesis of a novel series of 4-arylhydrazono-5-methyl-1,2-dihydropyrazol-3-ones 4a-h, and their N (2)-alkyl and acyclo, glucopyranosyl, and ribofuranosyl derivatives is described. K(2)CO(3) catalyzed alkylation of 4a-h with allyl bromide, propargyl bromide, 4-bromobutyl acetate, 2-acetoxyethoxymethyl bromide, and 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide proceeded selectively at the N (2)-position of the pyrazolinone ring. Glycosylation of 4a with 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose under Vorbruggen glycosylation conditions gave the corresponding N (2)-4-arylhydrazonopyrazolone ribofuranoside 9a in good yield.

Hydrogen bond formation between the naturally modified nucleobase and phosphate backbone.

Natural RNAs, especially tRNAs, are extensively modified to tailor structure and function diversities. Uracil is the most modified nucleobase among all natural nucleobases. Interestingly, >76% of uracil modifications are located on its 5-position.

Novel RNA base pair with higher specificity using single selenium atom.

Specificity of nucleobase pairing provides essential foundation for genetic information storage, replication, transcription and translation in all living organisms. However, the wobble base pairs, where U in RNA (or T in DNA) pairs with G instead of A, might compromise the high specificity of the base pairing. The U/G wobble pairing is ubiquitous in RNA, especially in non-coding RNA.

Synthesis and evaluation of the substrate activity of C-6 substituted purine ribosides with E. coli purine nucleoside phosphorylase: palladium mediated cross-coupling of organozinc halides with 6-chloropurine nucleosides.

A series of C-6 alkyl, cycloalkyl, and aryl-9-(β-d-ribofuranosyl)purines were synthesized and their substrate activities with Escherichia coli purine nucleoside phosphorylase (E. coli PNP) were evaluated. (Ph(3)P)(4)Pd-mediated cross-coupling reactions of 6-chloro-9-(2,3,5-tri-O-acetyl-β-d-ribofuranosyl)-purine (6) with primary alkyl (Me, Et, n-Pr, n-Bu, isoBu) zinc halides followed by treatment with NH(3)/MeOH gave the corresponding 6-alkyl-9-(β-d-ribofuranosyl)purine derivatives 7-11, respectively, in good yields.

Synthesis, structure and imaging of oligodeoxyribonucleotides with tellurium-nucleobase derivatization.

We report here the first synthesis of 5-phenyl-telluride-thymidine derivatives and the Te-phosphoramidite. We also report here the synthesis, structure and STM current-imaging studies of DNA oligonucleotides containing the nucleobases (thymine) derivatized with 5-phenyl-telluride functionality (5-Te). Our results show that the 5-Te-DNA is stable, and that the Te-DNA duplex has the thermo-stability similar to the corresponding native duplex.

High fidelity of base pairing by 2-selenothymidine in DNA.

The base pairs are the contributors to the sequence-dependent recognition of nucleic acids, genetic information storage, and high fidelity of DNA polymerase replication. However, the wobble base pairing, where T pairs with G instead of A, reduces specific base-pairing recognition and compromises the high fidelity of the enzymatic polymerization. Via the selenium atomic probing at the 2-position of thymidine, we have investigated the wobble discrimination by manipulating the steric and electronic effects at the 2-exo position, providing a unique chemical strategy to enhance the base pair specificity.

Synthesis of the first tellurium-derivatized oligonucleotides for structural and functional studies.

We report here the first synthesis of Te-nucleoside phosphoramidites and Te-modified oligonucleotides. We protected the 2'-tellurium functionality by alkylation and found that the Te functionality is compatible with solid-phase synthesis and that the Te oligonucleotides are stable during deprotection and purification. In addition, the redox properties of the Te functionalities have been explored.

Synthesis and crystallographic analysis of 5-Se-thymidine DNAs.

We investigated the possibility of the interaction of 5-CH(3) of thymidine and its 5'-phosphate backbone (C-H...