Nejvíce citovaný článek - PubMed ID 30273836
Pentamethinium salts as ligands for cancer: Sulfated polysaccharide co-receptors as possible therapeutic target
Mitochondrial dysregulation plays a significant role in the carcinogenesis. On the other hand, its destabilization strongly represses the viability and metastatic potential of cancer cells. Photodynamic and photothermal therapies (PDT and PTT) target mitochondria effectively, providing innovative and non-invasive anticancer therapeutic modalities. Cyanine dyes, with strong mitochondrial selectivity, show significant potential in enhancing PDT and PTT. The potential and limitations of cyanine dyes for mitochondrial PDT and PTT are discussed, along with their applications in combination therapies, theranostic techniques, and optimal delivery systems. Additionally, novel approaches for sonodynamic therapy using photoactive cyanine dyes are presented, highlighting advances in cancer treatment.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
IL-6 signaling is involved in the pathogenesis of a number of serious diseases, including chronic inflammation and cancer. Targeting of IL-6 receptor (IL-6R) by small molecules is therefore an intensively studied strategy in cancer treatment. We describe the design, synthesis, and characteristics of two new bis-pentamethinium salts 5 and 6 (meta and para) bearing indole moieties. Molecular docking studies showed that both compounds have the potential to bind IL-6R (free energy of binding -9.5 and -8.1 kcal/mol). The interaction with IL-6R was confirmed using microscale thermophoresis analyses, which revealed that both compounds had strong affinity for the IL-6R (experimentally determined dissociation constants 26.5 ± 2.5 nM and 304 ± 27.6 nM, respectively). In addition, both compounds were cytotoxic for a broad spectrum of cancer cell lines in micromolar concentrations, most likely due to their accumulation in mitochondria and inhibition of mitochondrial respiration. In summary, the structure motif of bis-pentamethinium salts represents a promising starting point for the design of novel multitargeting compounds with the potential to inhibit IL-6 signaling and simultaneously target mitochondrial metabolism in cancer cells.
- Klíčová slova
- IL-6R synthetic inhibitors, cancer, mitochondria,
- Publikační typ
- časopisecké články MeSH
This study presents a simple route to heparin detection and develops a voltammetric approach using supramolecular principles and nanomaterials. Nanocomposites, including gold nanoparticles (AuNPs) and γ-substituted pentamethinium salts (PMS) deposited on a glass carbon (GC) electrode surface (GC/AuNPs/PMS) and covered by a plasticized poly(vinyl chloride) (PVC) membrane, are proposed for heparin detection. The conductivity of the nonconducting PVC-plasticized membrane is guaranteed by AuNPs, and the selectivity is provided by the interaction between γ-substituted PMS and anionic analytes. In order to extend the linear range, it is necessary to apply a solvent compatible with PVC-plasticized membrane, namely tetrahydrofuran. The proposed voltammetric sensor showed a concentration dependence from 1.72 up to 45.02 IU mL-1 heparin and was used for heparin detection in saline and biological samples with recovery of 95.1-100.9%.
- Klíčová slova
- gold nanoparticles, heparin, nanocomposite, voltammetric sensor, γ-substituted pentamethinium salts,
- Publikační typ
- časopisecké články MeSH