The Lipophilic Purine Nucleoside-Tdp1 Inhibitor-Enhances DNA Damage Induced by Topotecan In Vitro and Potentiates the Antitumor Effect of Topotecan In Vivo.

The use of cancer chemotherapy sensitizers is a promising approach to induce the effect of clinically used anticancer treatments. One of the interesting targets is Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), a DNA-repair enzyme, that may prevent the action of clinical Topoisomerase 1 (Top1) inhibitors, such as topotecan (Tpc). Tdp1 eliminates covalent Top1-DNA (Top1c) complexes that appear under the action of topotecan and determines the cytotoxic effect of this drug.

In Planta, In Vitro and In Silico Studies of Chiral -Benzyladenine Derivatives: Discovery of Receptor-Specific -Enantiomers with Cytokinin or Anticytokinin Activities.

Cytokinins, classical phytohormones, affect all stages of plant ontogenesis, but their application in agriculture is limited because of the lack of appropriate ligands, including those specific for individual cytokinin receptors. In this work, a series of chiral -benzyladenine derivatives were studied as potential cytokinins or anticytokinins. All compounds contained a methyl group at the α-carbon atom of the benzyl moiety, making them - or -enantiomers.

Anticoagulant Oligonucleotide-Peptide Conjugates: Identification of Thrombin Aptamer Conjugates with Improved Characteristics.

Oligonucleotide-peptide conjugates (OPCs) are a promising class of biologically active compounds with proven potential for improving nucleic acid therapeutics. OPCs are commonly recognized as an efficient instrument to enhance the cellular delivery of therapeutic nucleic acids. In addition to this application field, OPCs have an as yet unexplored potential for the post-SELEX optimization of DNA aptamers.

Pre-Senescence Induction in Hepatoma Cells Favors Hepatitis C Virus Replication and Can Be Used in Exploring Antiviral Potential of Histone Deacetylase Inhibitors.

Recent evidence suggests that fibrotic liver injury in patients with chronic hepatitis C correlates with cellular senescence in damaged liver tissue. However, it is still unclear how senescence can affect replication of the hepatitis C virus (HCV). In this work, we report that an inhibitor of cyclin-dependent kinases 4/6, palbociclib, not only induced in hepatoma cells a pre-senescent cellular phenotype, including G1 arrest in the cell cycle, but also accelerated viral replicon multiplication.

Cytokinin activity of N-benzyladenine derivatives assayed by interaction with the receptors in planta, in vitro, and in silico.

Biological effects of hormones in both plants and animals are based on high-affinity interaction with cognate receptors resulting in their activation. The signal of cytokinins, classical plant hormones, is perceived in Arabidopsis by three homologous membrane receptors: AHK2, AHK3, and CRE1/AHK4. To study the cytokinin-receptor interaction, we used 25 derivatives of potent cytokinin N-benzyladenine (BA) with substituents in the purine heterocycle and/or in the side chain.

Fluorination of Naturally Occurring N⁶-Benzyladenosine Remarkably Increased Its Antiviral Activity and Selectivity.

Recently, we demonstrated that the natural cytokinin nucleosides ⁶-isopentenyladenosine () and ⁶-benzyladenosine () exert a potent and selective antiviral effect on the replication of human enterovirus 71. In order to further characterize the antiviral profile of this class of compounds, we generated a series of fluorinated derivatives of and evaluated their activity on the replication of human enterovirus 71 in a cytopathic effect (CPE) reduction assay. The monofluorination of the -phenyl group changed the selectivity index (SI) slightly because of the concomitant high cell toxicity.

New tools in nucleoside toolbox of tick-borne encephalitis virus reproduction inhibitors.

Design and development of nucleoside analogs is an established strategy in the antiviral drug discovery field. Nevertheless, for many viruses the coverage of structure-activity relationships (SAR) in the nucleoside chemical space is not sufficient. Here we present the nucleoside SAR exploration for tick-borne encephalitis virus (TBEV), a member of Flavivirus genus.

Modification of the length and structure of the linker of N(6)-benzyladenosine modulates its selective antiviral activity against enterovirus 71.

Very recently, we demonstrated that N(6)-isopentenyladenosine, a cytokinin nucleoside, exerts a potent and selective antiviral effect on the replication of human enterovirus 71. The present study is devoted to the structure optimization of another natural compound: N(6)-benzyladenosine. We mainly focused on the exploration of the size and nature of the linker between the adenine and the phenyl ring, as well as on the necessity of the D-ribose residue.