Therapeutic Responses to Two New SN-38 Derivatives in Colorectal Cancer Patient-Derived Xenografts and Respective 3D Cultures.

Background/aim: SN-38, an active metabolite of irinotecan, exhibits toxicity to all proliferating cells, causing dose-limiting and potentially life-threatening side effects. Newly established water-soluble derivatives of SN-38, 7-ethyl-9-(N-morpholinyl)methyl-10-hydroxycamptothecin (BN-MOA) and 7-ethyl-9-(N-methylamino)methyl-10-hydroxycamptothecin (BN-NMe), exhibit a unique mechanism of spontaneous alkylation of aromatic bases in DNA and show greater in vitro activity on cancer cell lines than SN-38. The aim of this study was to compare the therapeutic responses to irinotecan, BN-MOA and BN-NMe in vivo and in vitro in 3D cultures using colorectal cancer (CRC) patient derived xenografts (PDX).

New 5-Substituted SN38 Derivatives: A Stability Study and Interaction with Model Nicked DNA by NMR and Molecular Modeling Methods.

The new 5-substituted SN-38 derivatives, 5()-(N-pyrrolidinyl)methyl-7-ethyl-10-hydroxycamptothecin () and its diastereomer 5() (), were investigated using a combination of nuclear magnetic resonance (NMR) spectroscopy and molecular modeling methods. The chemical stability, configuration stability, and propensity to aggregate as a function of concentration were determined using H NMR. The calculated self-association constants () were found to be 6.

Insight on the Interaction between the Camptothecin Derivative and DNA Oligomer Mimicking the Target of Topo I Inhibitors.

The understanding of the mechanism of Topo I inhibition by organic ligands is a crucial source of information that has led to the design of more effective and safe pharmaceuticals in oncological chemotherapy. The vast number of inhibitors that have been studied in this respect over the last decades have enabled the creation of a concept of an 'interfacial inhibitor', thereby describing the machinery of Topo I inhibition. The central module of action of this machinery is the interface of a Topo I/DNA/inhibitor ternary complex.

Novel Nontoxic 5,9-Disubstituted SN38 Derivatives: Characterization of Their Pharmacological Properties and Interactions with DNA Oligomers.

Novel nontoxic derivatives of SN38 with favorable antineoplastic properties were characterized in water solution using NMR. The phenomena observed by NMR were linked to basic pharmacological properties, such as solubility, bioavailability, chemical and stereochemical stability, and binding to natural DNA oligomers through the terminal G-C base pair, which is commonly considered a biological target of Topo I inhibitors. Compound , with bulky substituents at both C5() and C20() on the same side of a camptothecin core, manifests self-association, whereas diastereomers , with bulky C5() and C20() substituents are mostly monomeric in solution.

The Mode of SN38 Derivatives Interacting with Nicked DNA Mimics Biological Targeting of Topo I Poisons.

The compounds 7-ethyl-9-(-methylamino)methyl-10-hydroxycamptothecin () and 7-ethyl-9-(-morpholino)methyl-10-hydroxycamptothecin () are potential topoisomerase I poisons. Moreover, they were shown to have favorable anti-neoplastic effects on several tumor cell lines. Due to these properties, the compounds are being considered for advancement to the preclinical development stage.

New camptothecin derivatives for generalized oncological chemotherapy: Synthesis, stereochemistry and biology.

Derivatives of SN38 were synthesized that were either monosubstituted at C-5 or C-9 or disubstituted at both C-5 and C-9. Substitution to C-5 led to the generation of pairs of diastereomers (2c-2 h) in a one-pot reaction and was readily separable by HPLC. The absolute configurations of C-5 were established by electronic circular dichroism experiments.

Bioinspired Bola-Type Peptide Dendrimers Inhibit Proliferation and Invasiveness of Glioblastoma Cells in a Manner Dependent on Their Structure and Amphipathic Properties.

(1) Background: Natural peptides supporting the innate immune system studied at the functional and mechanistic level are a rich source of innovative compounds for application in human therapy. Increasing evidence indicates that apart from antimicrobial activity, some of them exhibit selective cytotoxicity towards tumor cells. Their cationic, amphipathic structure enables interactions with the negatively-charged membranes of microbial or malignant cells.

A comparative study of the performance of passive samplers.

Atmospheric concentrations of benzene, toluene, ethylbenzene, and xylenes (o-xylene and m,p-xylene) were assessed in the Tricity area (Gdańsk-Sopot-Gdynia, Poland) with the use of two types of passive samplers: permeation (homemade passive samplers) and diffusive (Radiello and Orsa 5). Samples were collected during 2008 at selected sites in the Tricity area at monitoring stations belonging to the agency of Regional Air Quality Monitoring Foundation. The field study was conducted to compare the performance of these two different types of passive samplers.

Solventless sample preparation techniques based on solid- and vapour-phase extraction.

The main objective of this review is to critically evaluate recent developments in solventless sample preparation techniques. The potential of a variety of sample preparation techniques based on solid- and vapour-phase extraction techniques is evaluated. Direct thermal extraction and derivatization processes to facilitate the extraction of analytes in different areas are included.

Spatial and seasonal patterns of benzene, toluene, ethylbenzene, and xylenes in the Gdansk, Poland and surrounding areas determined using radiello passive samplers.

Atmospheric concentrations of benzene, toluene, ethylbenzene, and xylenes (BTEX) were assessed in the Gdańsk-Sopot-Gdynia Tricity area and in the city of Tczew using diffusive-type Radiello passive samplers. Samples were collected at the monitoring stations belonging to the Agency of Regional Air Quality Monitoring Foundation. The results indicated that the BTEX concentrations measured in the urban air in the Tricity area and in Tczew were dependent on the season, being somewhat higher in winter and spring than in summer.

Application of passive sampling technique for monitoring of BTEX concentration in urban air: field comparison of different types of passive samplers.

Urban air background concentrations of benzene, toluene, ethylbenzene, and xylenes (BTEX) were measured in 2007 in the Tricity area (Gdansk, Gdynia, and Sopot) and Tczew applying two types of passive samplers: Home-made permeation passive samplers and two diffusive passive samplers Orsa 5 (National Dräger) and Radiello (FS Maugeri). Differences between the time-weighted annual averages concentrations of BTEX obtained with two types of passive samplers were found in each of the sampling sites. The obtained results indicate that the BTEX concentrations measured in the urban air in the Tricity area and Tczew are slightly dependent on season; they are higher in winter and spring than in summer.

Passive sampling as a tool for obtaining reliable analytical information in environmental quality monitoring.

Passive sampling technology has been developing very quickly for the past 20 years, and is widely used for monitoring pollutants in different environments, for example air, water, and soil. It has many significant advantages, including simplicity, low cost, no need for expensive and complicated equipment, no power requirements, unattended operation, and the ability to produce accurate results. The present generation of passive samplers enables detection and analysis of bioavailable pollutants at low and very low concentrations and investigation of the environmental concentration of organic and inorganic pollutants not only on the local scale but also on continental and global scales.

Advances in passive sampling in environmental studies.

Passive sampling is based on the phenomenon of mass transport due to the difference between chemical potentials of analytes in a given environmental compartment and the collection medium inside a dosimeter. The subsequent laboratory procedure (i.e.