Vol 49, No 12 (2016)

Methods of obtaining biotinylated oxidized dextran (BTOD) and procedures for pharmacokinetic studies of BTOD and biotinylated dextran (BTD) are described. The pharmacokinetics results showed that there are no differences in principle between the oxidized and unoxidized dextrans. All studied dextrans were characterized by two-phase pharmacokinetic profiles after intraperitoneal and subcutaneous administration.

A series of 2-phenoxy-N-phenylacetamides were designed and synthesized with a view to develop novel anticancer agents. All compounds were prepared with varied substitutions in the phenyl ring of aniline and evaluated for their anticancer activity. The majority of them displayed a moderate degree of cytotoxicity against several human cancer cell lines. Six compounds displayed potent cell growth inhibitory activity with IC₅₀ values below 20 μM. Two compounds (TC-5 and TC-14) exhibited the most pronounced antiproliferative activity equivalent to or higher than that of positive control. The structure – activity relationship of these anticancer agents has been reviewed. The results indicate that incorporation of halogen into the benzene ring is beneficial for anticancer activity.

Nanoparticles of the steroidal hormone dihydroepiandrosterone (DHEA) were prepared by cryosynthesis technology, which allowed starting DHEA particles of size (100 ± 50) μm to be converted to nanoparticles of size (100 ± 20) nm. The particle sizes were determined by optical, electron transmission, and scanning atomic-force microscopy. HPLC with mass-spectrometric detection of starting and modified DHEA samples showed that the hormone molecular structure did not change during cryosynthesis of the nanoparticles. A comparison of the cytotoxicities of the samples on C6 glial cell culture showed that modified DHEA was less toxic. The results indicated that cryosynthesis technology could be used effectively to prepare nanoparticles of steroidal hormones.

An impurity in rimantadine hydrochloride drug substance that was previously undescribed in regulatory documents and the literature was identified. Its structure was elucidated and confirmed by a convergent synthesis. A method for synthesizing bis-[1-(adamantan-1-yl)ethyl]amine hydrochloride under laboratory conditions was developed. The antibacterial activity of the synthesized compound was assessed.

New methods for synthesizing pyrano[3,4-b ]furo[2,3-b]pyridine derivatives from 7,7-dimethyl-2-oxo-3-cyano-1,2,7,8-tetrahydro-5H-pyrano[4,3-b ]pyridine were developed. Their neurotropic activity was investigated.

Optical absorption spectroscopy (OAS) is used in Ukraine mainly for laboratory quality control of medicines. This technique is introduced into regulatory analytical documentation only when the permissible limit of drug substance in the medicine is at least ± 10%. Results from validation tests in two different laboratories of three batches of prednisolone substance were assessed in order to determine the correctness of using OAS for its pharmacopoeial analysis. The practical uncertainty of the OAS spectrophotometric analytical technique for each sample of prednisolone substance analyzed individually in the two laboratories was less than the regulated critical tolerance of ± 3% according to the State Pharmacopoeia of Ukraine. The results allowed the OAS method to be recommended for quality control of prednisolone substance provided the equipment is qualified and the correctness of the results is controlled.

The development of drug resistant strains of pathogenic fungi despite the availability of a large number of drugs demands for the development of new, more potential drug molecules. Dendrimer-based drug molecules have been comparatively less studied upon recent advancement in this field. In the present work, a new water-soluble dendritic ligand and its copper(II), nickel(II), and cobalt(II) complexes have been synthesized. The ligand, as well as its complexes, were characterized by various physicochemical, analytical, and spectroscopic techniques. On the basis of UV-Vis spectroscopic data, tetragonal geometry was proposed for Cu(II) complex and square planar geometry was established for Co(II) and Ni(II) complexes. The antifungal activities of water-soluble compounds were evaluated using the disk diffusion method, and the minimal inhibitory concentrations (MICs) against Candida albicans ATCC 90028 were determined by the dilution method. The synthesized compounds proved to be fungicidal in comparison to fluconazole, which is fungistatic only; however, these compounds were less active than fluconazole. Hemolysis assays for one of the reported compound showed that it was nontoxic in comparison to fluconazole. Therefore, the proposed compounds can serve as promising leads for the development of new antifungal agents.

New azacytidine nucleoside analogs with modified carbohydrate moieties were synthesized. Screening identified a highly active 2′-fluoro-containing azacytidine analog that could potentially be of interest as an agent for treating acute myelogenous leukemia and myelodysplastic syndrome.

Total flavonoids from Vexibia alopecuroides administered for two weeks to rats with alloxan diabetes lowered the blood glucose level and increased the lactic-pyruvic acid redox potential and liver glycogen level. Lipid metabolism, the antioxidant protection system, and peroxidation processes showed a distinct tendency to normalize in vivo through the influence of the total flavonoids. In this respect, total flavonoids from V. alopecuroides were as effective in the conducted experiments as the known anti-diabetes agent diabeton.

An HPLC method over a Kromasil C18 reversed-phase column with mass spectrometric detection and EtOH:NH₄OAc (10:90) mobile phase was developed for quantitative determination of the antitumor drug ormustine in biological fluids. The method enabled detection of both drug isomers, possessed sufficiently high sensitivity and specificity, and was linear over a wide range. The developed method was used to study ormustine pharmacokinetics in rabbits. It was found that the pharmacokinetics of both drug isomers after i.v. injection followed a two-compartment model. The elimination half-lives of ormustine-I were (3.5 ± 0.2) and (109.4 ± 22.2) min for the α- and β-phases, respectively; of ormustine-II, (3.6 ± 0.2) and (79.5 ± 21.7) min, respectively.