Verubulin (Azixa) Analogues with Increased Saturation: Synthesis, SAR and Encapsulation in Biocompatible Nanocontainers Based on Ca2+ or Mg2+ Cross-Linked Alginate.

Tubulin-targeting agents attract undiminished attention as promising compounds for the design of anti-cancer drugs. Verubulin is a potent tubulin polymerization inhibitor, binding to colchicine-binding sites. In the present work, a series of verubulin analogues containing a cyclohexane or cycloheptane ring 1,2-annulated with pyrimidine moiety and various substituents in positions 2 and 4 of pyrimidine were obtained and their cytotoxicity towards cancer and non-cancerous cell lines was estimated. The investigated compounds revealed activity against various cancer cell lines with IC50 down to 1-4 nM. According to fluorescent microscopy data, compounds that showed cytotoxicity in the MTT test disrupt the normal cytoskeleton of the cell in a pattern similar to that for combretastatin A-4. The hit compound (N-(4-methoxyphenyl)-N,2-dimethyl-5,6,7,8-tetrahydroquinazolin-4-amine) was encapsulated in biocompatible nanocontainers based on Ca2+ or Mg2+ cross-linked alginate and it was demonstrated that its cytotoxic activity was preserved after encapsulation.

One-Step Low Temperature Synthesis of CeO2 Nanoparticles Stabilized by Carboxymethylcellulose.

An elegant method of one-pot reaction at room temperature for the synthesis of nanocomposites consisting of cerium containing nanoparticles stabilized by carboxymethyl cellulose (CMC) macromolecules was introduced. The characterization of the nanocomposites was carried out with a combination of microscopy, XRD, and IR spectroscopy analysis. The type of crystal structure of inorganic nanoparticles corresponding to CeO2 was determined and the mechanism of nanoparticle formation was suggested. It was demonstrated that the size and shape of the nanoparticles in the resulting nanocomposites does not depend on the ratio of the initial reagents. Spherical particles with a mean diameter 2-3 nm of were obtained in different reaction mixtures with a mass fraction of cerium from 6.4 to 14.1%. The scheme of the dual stabilization of CeO2 nanoparticles with carboxylate and hydroxyl groups of CMC was proposed. These findings demonstrate that the suggested easily reproducible technique is promising for the large-scale development of nanoceria-containing materials.