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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.

Synthetic and natural polymers are widely used for constructing drug delivery systems. Biocompatibility, water solubility and non-toxicity make polymers a convenient matrix for encapsulation, delivery and release of bioactive compounds. Coupling of a drug with a biodegraded polymer matrix is a promising way for a controlled drug delivery. Along this line, the degradation of the four polymers in the presence of two enzymes in aqueous solutions was investigated. The following polymers were used: natural polysaccharides, sodium alginate and sodium hyaluronate, artificial (modified) sodium carboxymethylcellulose and synthetic sodium polyacrylate (control); their degradation was caused by the addition of alginate lyase and hyaluronidase. The first enzyme only cleaved the specific alginate substrate and left three other intact. Contrastingly, the second enzyme degraded all three polysaccharides, including artificial carboxymethylcellulose, but did not degrade synthetic polyacrylate. The biodegradation of polymers was accompanied by decreasing the size of polymer particles in solution from 100 to 200 nm down to 20-30 nm; the latter are capable of removing from the body through the kidneys. The initial polysaccharides showed the negative surface charge in aqueous solution, which changed but retained negative after biodegradation. The initial and biodegraded polysaccharides demonstrated negligible cytotoxicity during long exposure period. The obtained results are valuable for the development of polymer carriers for drug encapsulation and delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The controllable delivery of drugs is a key task of pharmacology. For this purpose, a series of polymer composites was synthesized via the cross-linking of hyaluronate and a hyaluronate/polyacrylate mixture with Fe 2 O 3 nanoparticles. The cross-linking imparts magnetic properties to the composites, which are more pronounced for the ternary hyaluronate/polyacrylate/γ-Fe 2 O 3 composites compared with the binary hyaluronate/Fe 2 O 3 composites. When dispersed in water, the composites produce microsized hydrogel particles. Circulation of the ternary microgels in an aqueous solution at a speed of 1.84 cm/s can be stopped using a permanent external magnet with a magnetic flux density of 400 T. The composite hydrogels can absorb the antitumor antibiotic doxorubicin (Dox); the resulting constructs show their cytotoxicity to tumor cells to be comparable to the cytotoxicity of Dox itself. The addition of the hyaluronidase enzyme induces degradation of the binary and ternary microgels down to smaller particles. This study presents prospectives for the preparation of magnetically controlled biodegradable polymer carriers for the encapsulation of bioactive substances.