Vol 50, No 11 (2017)

Previously designed cyclo-L-prolylglycine (CPG), a peptide prototype of piracetam, was discovered as an endogenous compound in rat brain and exhibited nootropic and anxiolytic properties. N-Phenylacetylglycyl-L-proline ethyl ester (GZK-111) was synthesized in the present work. It was established that GZK-111 converted to CPG and possessed nootropic, anxiolytic, and antihypoxic activities typical of CPG at doses of 0.1 – 1.5 mg/kg (i.p.). The effects of both GZK-111 and CPG were stereoselective with only the L-enantiomers being active. GZK-111 could be considered as a prodrug that enhanced cognitive functioning with an anxiolytic component.

N-Succinylchitosan (SC) with degree of substitution 0.86 was prepared by reacting chitosan with succinic anhydride. The otoprotective potential of a single i.v. injection of a solution (0.3%) of the sodium salt of SC in 60 rats (males, Wistar, 220 – 250 g) was studied. A solution of meglumine sodium succinate (MSS) at an equivalent concentration was used as a reference. The drugs were administered 2 h or 5 min prior to induction of acute injury of the auditory analyzer by acoustic stimulation (AS). The condition of hearing was estimated by studying optoacoustic emission (OAE) at the frequency of distortion product 1 h, 24 h, and 7 d after the AS. SC showed a more pronounced protective effect with early preventive administration (p < 0.02; ANOVA with Bonferroni correction). Conversely, MSS exhibited its protective properties only with immediate administration. A comparison of the two drug administration modes showed that the OAE amplitude was depressed more after MSS administration than after SC injection (p < 0.05; Tukey’s test). It was concluded that conjugation to chitosan prolonged the elimination half-life of succinate and improved its access to cochlear back-barrier tissues.

Acylation of 1-piperidinocyclopentene by aromatic and arylacetic acid chlorides synthesized the corresponding 1,3-diketones that were reacted with hydrazine hydrate to give 3-aryl- and 3-arylmethylcyclopenta[c]pyrazoles and with hydroxylamine to give the corresponding cyclopenta[d]isoxazoles. The diketones and heterocyclic compounds prepared from them exhibited weak inhibitory activity against Staphylococcus aureus and Escherichia coli. The starting diketone containing a p-NO₂ group was the most active compound with a minimum inhibitory concentration of 125 μg/mL.

A production technology using vortex extraction, baromembrane methods, and spray drying was developed for obtaining increased yields of katatsin drug substance from roots of Polygonum coriarium Grig.

New lifestyle is the main reason of diseases related to high blood glucose and lipid levels. Treatment by chemical drugs is common way for the remedy of these illnesses, which is replaced by application of medicinal plants. Vaccinum arctostaphylos fruits have been used extensively as traditional medicines for treatment of diabetic and lipidemic symptoms. These fruits have additional health benefits as they are rich in phytochemicals such as flavonoids and polyphenols, which have been reported to possess many pharmacological activities. In this research, the effect of solvent polarity on bioactive extract yield from unripe fruits of this plant was evaluated by GC-MS analysis. Then, antidiabetic and antilipidemic properties of different extracts were investigated in rats with streptozotocin-induced diabetes and compared to glibenclamide as reference chemical drug for diabetes. The results indicate that all extracts (particulaly, carbon tetrachloride extract) produce significant decrease in blood glucose and lipid levels, which can be related to the high content of fatty acids, sterols, phenolics, and unsaturated alcohols in these extracts.

Sulfonyl chlorides were synthesized from pyrazoles via sulfonation by chlorosulfonic acid. The optimum conditions for synthesizing pyrazolesulfonyl chlorides in preparative yields were determined.

The compositions of lipids and lipophilic constituents from seeds of Symphytum officinale L. (Boraginaceae Juss., comfrey) were studied. Neutral and polar lipids were identified and quantified. The fatty-acid composition was determined. It was found that the greatest amounts of polyunsaturated fatty acids (PUFA) were concentrated in total NL (57.6%, including 16% γ-linolenic acid) and triacylglycerides (56.5%). A fraction with 99% PUFA, including 72% γ-linolenic acid, was obtained as clathrates with urea. Lipophilic constituents, i.e., sterols, were identified.

Comparative analysis of the primary structure of recombinant human follicle-stimulating hormone (r-hFSH) in samples of follitropin alpha biosimilar (FAB) preparation and the reference drug Gonal-F showed they were identical while spectral analysis of their secondary and tertiary structures indicated they were bioequivalent. Analytical results for N-glycans and sialic acids revealed that the main glycan structures were similar and the distributions of the main forms of sialic acids in the compared samples differed insignificantly. Results of in vitro and in vivo biological activity testing confirmed that FAB and Gonal-F were equivalent with respect to WHO standards. Comparative testing of the acute and subacute toxicity did not reveal significant differences between the two drugs and also confirmed they were identical. Thus, the investigation proved that FAB and the reference drug were equivalent with respect to the main physicochemical, pharmacodynamic, and toxicological characteristics.

Technology for the synthesis of S-amlodipine nicotinate drug substance was developed based on an acceptable method of effective separation of the amlodipine optical isomers. A literature review suggested that the most promising methods employed 2-propanol (pure or with small additions of cosolvents) as the main solvent. However, experiments showed that the optimum solvent was DMSO. The proposed synthesis of S-amlodipine nicotinate drug substance was confirmed to be stable and reproducible. Standardization methods were developed.

The literature on the most frequently used methods for quantitative determination of coenzyme Q₁₀ in biological materials was reviewed. HPLC in combination with electrochemical detection had the advantage among spectrophotometric, electrochemical, and chromatographic methods owing to high selectivity and sensitivity and the availability of modern detectors.