calixarenes and thiazolyl-blue

Beta1,4-Galactosyltransferases (beta1,4-GalTase) exposed on the cell surface are involved in cell migration. Specifically, beta1,4-GalTase V is highly expressed in glioma and promotes invasion, growth, and survival of glioma cells. A glycocalix[8]arene exposing N-acetylglucosamine (GlcNAc) residues (compound 1) inhibited rat C6 glioma cell migration as assessed in a scratch wound model. This effect was related to inhibition of focal adhesion kinase phosphorylation, measured by western blot analysis, and specifically observed in the area bordering the scratch wound. Compound 1 inhibited also C6 cell proliferation, an effect unrelated to its ability to interact with GalTase as it was mimicked by different calix[8]arene derivatives, all characterized by multivalency and ureido groups. Compound 1 did not induce apoptotic death, but caused a different distribution of C6 cells within the cell cycle. The results here reported identify compound 1 as a molecule able to exert inhibitory effects on C6 cell migration and proliferation, independently, because of distinct components in its structure.

Topics: Analysis of Variance; Animals; Benzimidazoles; Bromodeoxyuridine; Calixarenes; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cyclopentanes; Enzyme Activation; Focal Adhesion Kinase 1; Glioma; N-Acetylgalactosaminyltransferases; Rats; Tetrazolium Salts; Thiazoles; Time Factors; Wounds and Injuries

Emergence of multidrug-resistant bacteria has encouraged vigorous efforts to develop antimicrobial agents with new mechanisms of action. In this study, the in vitro antibacterial activity of para-guanidinoethylcalix[4]arene was evaluated and compared with that of its constitutive monomer, para-guanidinoethylphenol. Hexamidine, a widely used antiseptic, and synthalin A, an old antidiabetic and anti-trypanosomal compound, were chosen as references.. MIC and MBC were determined for five reference strains (Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and ATCC 29213, Enterococcus faecalis ATCC 29212 and Pseudomonas aeruginosa ATCC 27853), as well as five antibiotic-resistant clinical isolates. Toxicity on MRC-5 and HaCaT eukaryotic cell lines was also evaluated by MTT and Neutral Red assays.. No antibacterial activity was observed for para-guanidinoethylphenol (MIC >or= 512 mg/L) and synthalin A (MIC >or= 64 mg/L). Conversely, para-guanidinoethylcalix[4]arene and hexamidine: (i) showed a broad antibacterial spectrum, both on Gram-positive and on Gram-negative bacteria (MIC = 4 mg/L against E. coli and 8 mg/L against S. aureus for para-guanidinoethylcalix[4]arene), to a lesser degree against E. faecalis and P. aeruginosa (MIC = 32 mg/L); (ii) were bacteriostatic (MBC >or= 256 mg/L); and (iii) MICs and MBCs obtained for clinical isolates were similar to those obtained with reference strains. Both compounds, the monomer and the calixarene, showed no apparent cytotoxicity, whereas hexamidine and synthalin A had significant toxic effects that increased with time and concentration and in a range of 100-1000 times that for calixarene.. In conclusion, results confirm para-guanidinoethylcalix[4]arene as a broad-spectrum new agent or an auxiliary in antimicrobial chemotherapy.

Topics: Anti-Bacterial Agents; Benzamidines; Calixarenes; Cell Line, Tumor; Cell Survival; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Guanidines; Humans; Microbial Sensitivity Tests; Neutral Red; Structure-Activity Relationship; Tetrazolium Salts; Thiazoles