Vol 50, No 5 (2016)

The various types of pharmacological activity of 4,5-dihydropyrazole derivatives are reviewed. Attention is focused on the influence of various substituents in the dihydropyrazole core on the pharmacological effects of these compounds.

Methods for synthesizing novel amino derivatives of cyclopenta[4′,5′]pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines and tetrahydropyrimido[4′,5′:4,5]thieno[2,3-c]isoquinoline from 3-chloro derivatives of alicyclo[c]pyridines were elaborated. Studies of the anticonvulsant activity of the synthesized compounds showed that they exhibited pronounced anticonvulsant activity and low toxicity.

The antibacterial activity of several groups of substituted mono- and diatomic phenols and their derivatives with various structural parameters was studied. An analysis of the results allowed the activity to be attributed to particular structural elements of the tested compounds.

A micellar electrokinetic chromatographic method for quantitative determination of sesquiterpene lactones (costunolide and dehydrocostuslactone) from Laurus nobilis leaves was developed. It was shown that urea had to be added to the leading electrolyte in order to increase the analysis selectivity. The developed method was used to establish the costunolide and dehydrocostuslactone contents in various leaf samples as 0.5757 and 0.0399%, respectively, calculated per absolute dry raw material. The main validation characteristics of the developed method were also determined.

1,2-dihydro-3-methyl-2-oxoquinoxaline-6-carboxylic acid (S1) was prepared and coupled with various amino acid tri/tetrapeptide methyl esters to afford new quinoxalopeptide derivatives (S1a – S1i). The synthesized derivatives were characterized and screened for their antibacterial, antifungal and anthelmintic activity. Furthermore, molecular docking study revealed their potential in targeting human papillomavirus (HPV-16) E6 oncoprotein.

Phytoecdysteroids (at doses of 5 and 15 mg/kg of body mass per day) in the aqueous extract of Serratula coronata L. were administered toWistar rats for 15 d, did not have adverse effects on the thymus, and did not increase apoptosis rat in heart, brain, and thymus cells. The apoptosis rate in thymus cells of animals exposed to an electric shock increased statistically significantly relative to intact controls. The thymus mass did not decrease statistically significantly in stressed rats that received the phytoecdysteroid extract as compared with stressed animals that did not receive it. The apoptosis rate characterized by the DNA-damage level and number of apoptotic cells was also diminished in the thymus of stressed rats that received the extract. The results confirmed the safety of using phytoecdysteroid extracts in food and indicated that this extract inhibited the general adaptation syndrome of the rats.

Four pharmaceutical compositions for oral use that contained the dipeptide anxiolytic GB-115 as the active ingredient underwent preclinical trials in male laboratory white rats. Various excipients added to the compositions and their preparation technologies had significant effects on the dipeptide pharmacokinetics. It was shown that compositions 2 and 4 had advantages according to the main pharmacokinetic characteristics reflecting the bioavailability of GB-115. The pharmacological activities of GB-115 compositions 1 – 4 at oral doses of 0.3 – 0.9 mg/kg were studied in an elevated plus-maze (EPM) test. It was established that composition 4, which included micronized substance and a hydrophilic matrix with controlled release of the active ingredient (hydroxypropylmethylcellulose), possessed the highest anxiolytic activity and increased the residence time in the EPM open arms at doses of 0.3 mg/kg (p < 0.01) and 0.9 mg/kg (p < 0.01) as compared with the placebo group. Pharmaceutical composition 4 could be recommended for creating a controlled-release solid dosage form based on the comprehensive studies.

General analytical trends and approaches to quantitative determination of atypical neuroleptics (antipsychotics) in biological matrices were presented. Various analytical methods and sample preparation procedures for quantitative chemical analysis of these compounds were described.