Vol 51, No 10 (2018)

Current approaches to the search for new kappa-opioid receptor (κ-OR) agonists with potential analgesic activity are reviewed. Agents with peripheral activity and biased agonists are most promising for development. Signal events initiated by κ-OR activation are considered. Chemical structures of presently known κ-OR agonists are presented.

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely applied as magnetic resonance imaging (MRI) contrast agents and drug carriers in drug delivery systems (DDSs) for diagnostics and treatment of diseases. Observation of drug delivery, drug release, and monitoring of the treatment can be performed by MRI. Magnetic nanoparticles (MNPs) can be used as dual-mode agents for simultaneous MRI contrast and drug delivery. Application of dual-mode MRI-contrast and drug-carrier agent is especially useful in targeted DDS. In this study, we report on the preparation of captopril-coated MNPs as a new dual-mode agent for simultaneous MRI contrast and DDS. The influence of contrast agent on the longitudinal (T1) and transverse (T2, T2*) relaxation times was studied and it was found that the effect on T2 and T2* exceeds the effect on T1, which leads to darkening of the MR image. Release of captopril from γ-Fe₂O₃@SiO₂@captopril system was studied at three pH values and it was established that the drug release at pH 1.2 was greater than that at pH 4.8 and 7.4. The obtained results show that MNPs loaded with captopril can be used as dual-mode MRI contrast agent and DDS system.

A series of β-p-toluylacrylate salts with various amines that retained the molecular fragment responsible for the antibacterial activity were synthesized. A new efficient method for obtaining β-aroylvinyl-1-pyridinium and -triphenylphosphonium bromides was proposed. Antibacterial testing showed that all investigated compounds possessed antibacterial properties.

A complex of fullerene C₆₀ and dihydroquercetin (DHQC) was synthesized. Its biological activity in a model system was studied using chemiluminometry. It was established that the C₆₀/DHQC complex possessed antioxidant activity, which prompted further investigation of its biological effects. The structure of the complex will be elucidated in a continuation of this work using analytical HPLC and NMR spectroscopy.

A new dinuclear cobalt(III) compound [Co₂ (2,2′-azinodimethyldiphenol)₃] has been synthesized, which shows better cytotoxic activity than carboplatin and exhibits potent in vitro antiproliferative activity.

A series of β -ionone-derived curcumin analogs (1a – 1j) have been synthesized by condensation of β -ionone with a variety of aldehydes. The synthesized compounds were screened for their in vitro anti-inflammatory activity against lipopolysaccharide (LPS)-induced expression of the pro-inflammatory cytokines tumor necrosis factor- α (TNF- α) and interleukin-6 (IL-6). Five active compounds exhibited dose-dependent inhibition of the release of TNF-α and IL-6. The active analogs represent a new class of anti-inflammatory agents with improved potency as compared to curcumin. Furthermore, the active compound 1e showed a protective effect against LPS-induced septic mortality in vivo. Our results suggest that the obtained analogs may be further developed as potential agents for the prevention and treatment of inflammatory diseases.

An economic and rapid procedure for identification and quantitative determination of ascorbic acid using high-performance thin-layer chromatography (HPTLC) was developed. The optimum conditions for chromatography of vitamin C on a thin layer of absorbent with quantitative interpretation of the HPTLC data were established experimentally and justified theoretically. The proposed procedure was validated using medicinal plant raw materials such as nettle leaves and sea-buckthorn fruit. The procedure could be used for quality control of substances, single-component and complex preparations, plant materials, biologically active supplements, premixes, and products of the food and cosmetics industries.

Antiradical and hemorheological activities of conjugates synthesized from 2,6-diisobornyl-4-methylphenol (dibornol) and polysaccharides [inulin, carboxymethylcellulose, hydroxyethyl starch (HES)] were studied in vitro. The dibornol—HES polymer conjugate exhibited the greatest antiradical activity of the tested compounds for the water-soluble stable radical ABTS^•+ and limited statistically significantly the blood viscosity increase in an in vitro blood hyperviscosity model at a final concentration of 10^–5 g/ml of blood.

The first author’s affiliation should read Faculty of Science, Department of Chemistry, University of Maragheh, Maragheh, Iran.

Extracts of S. maximum and S. telephium showed antimicrobial activity against Staphylococcus aureus ATCC 6538P, Pseudomonas aeruginosa ATCC 27835, and Escherichia coli ATCC 25922. The EtOH extract of S. maximum that was not purified by CHCl₃ was most efficacious. The flavonoid contents in the extracts and their antimicrobial activities were correlated.

A synthetic 2-arylaminopyrimidine derivative (analog of imatinib mesylate) was incorporated into multilayer polyelectrolyte microcapsules prepared by alternating adsorption of protamine sulfate and pectin-Ag nanocomposite. The encapsulation effectiveness (EE) from an aqueous solution of the compound (4 mg/mL) was ~70% and reached 28 mass%. The release kinetics from the microcapsules depended significantly on the solution pH and ionic strength. Release of the imatinib analog was prolonged most in alkaline solutions. In vitro experiments on hemoblast suspension cultures showed that microencapsulation of the 2-arylaminopyrimidine derivative changed its antitumor activity and lowered the IC₅₀ value by 1.4 – 2.2 times.

Approaches to certification of substances as reference standards (RSs) by the mass-balance method and the restrictions that must be considered when using this method are considered. Formulas for estimating the uncertainty of certified values are presented. Also, formulas missing from the literature are given to assess a) the uncertainty in the contents of organic impurities obtained by normalization of peak areas (heights) with correction factors and b) the uncertainty in the detection limits of the organic impurities. Recommendations for correct certification of reference standards by the mass-balance method are provided.