Vol 52, No 5 (2018)

A series of 2-(4-trifluoromethylphenyl)- and 2-trifluoromethyl-9-dialkylaminoalkylimidazo[1,2-a]benzimidazoles were synthesized for the first time by reacting 2-amino-1-dialkylaminoalkylbenzimidazoles and 2-bromo-1-[(4-trifluoromethyl)phenyl]ethanone or 1-bromo-3,3,3-trifluoroacetone and were tested for analgesic and antiplatelet activity, glycogen phosphorylase and dipeptidyl peptidase-4 inhibitory activity, and in vitro glycation of bovine serum albumin.

A series of indole-containing γ-aminobutyric acids (GABA) were synthesized via alkaline hydrolysis of 4-(indol-3-yl)-2-pyrrolidones. Their structures were confirmed by IR, PMR, and ¹³C NMR spectroscopy. Studies of the pharmacological properties of 4-amino-3-indolylbutanoic acids (GABA derivatives) showed that they possessed neuropsychotropic activity, the spectrum of which depended on the acid molecular structure. Nootropic properties prevailed for 4-amino-3-(indol-3-yl)butanoic acid; anxiolytic activity, for 4-amino-3-(1-benzylindol-3-yl)butanoic acid.

1-Chloromethyl- and 1-dichloromethyl-3,3-dialkyl-3,4-dihydroisoquinolines were synthesized via cyclo-condensation of dialkylbenzylcarbinols with chloroacetonitrile or dichloroacetonitrile. Their hydrochlorides were tested for antiarrhythmic, anticonvulsant, and analgesic activity. Water-soluble 1-chloromethylisoquinoline hydrochlorides showed antiarrhythmic activity with a maximum antiarrhythmic index of 14.8. These same compounds were active against corazole-induced convulsions. 1-Dichloromethylisoquinolines had analgesic effects comparable with that of metamizole sodium.

Reformatsky reactions of dicarboxylic acid anhydrides formed monomethyl esters of oxodicarboxylic acids with antinociceptive and anti-inflammatory activity.

4-Aryl-2-[(2-oxo-1,2-diphenylethylidene)hydrazinyl]-4-oxobut-2-enoic-acid amides were produced via decyclization of 3-[(2-oxo-1,2-diphenylethylidene)hydrazono]-5-arylfuran-2(3H)-ones by the corresponding amines and via reaction of 4-aryl-2-hydroxy-4-oxobut-2-enoic-acid hetarylamides with 2-hydrazono-1,2-diphenylethanone. Their analgesic and antibacterial activities were studied. Compounds with low toxicities and activities comparable to and exceeding those of reference drugs were discovered.

In view of considerable interest in the design and synthesis of new heterocyclic compounds with promising biological activities for medical and biological applications, a series of eight imine derivatives have been synthesized through microwave-assisted Schiff base formation by reacting 2-(4-methoxyphenyl)acetohydrazide (3) and 4-amino-3-(4-methoxybenzyl)-1H-1,2,4-triazole-5(4H)-thione (6) with various substituted aldehydes. Structures of the newly synthesized compounds were characterized by FT-IR, ¹H NMR and ¹³C NMR spectral analysis. All the synthesized derivatives were screened for their in vivo anti-inflammatory and in vitro anti-oxidant activities using carrageenan induced rat paw edema test and DPPH free radical scavenging assay, respectively. In addition, molecular docking experiment was also performed to check the actual binding affinity of ligand against target protein. Compounds 4a, 4c, 7a, and 7c screened as potent anti-inflammatory drugs significantly lowered the volume of rat paw edema (P < 0.05). In case of anti-oxidant assay, compound 7a with ferrocenyl group as substituent R and 3,4-disubstitued 1,2,4-triazole as side coupled group exhibited IC₅₀ value of 7.2 ± 2.7 μg/mL comparable with that of the reference ascorbic acid (2.61 ± 0.29 μg/mL) and was the most active compound among the series. However, no prominent results were obtained in case of aralkanoic acid hydrazide substituted Schiff base derivatives 4a – 4d. It is believed that the synthesized Schiff base derivatives can be used for the development of potent anti-inflammatory and anti-oxidant drugs with considerable advantages of convenient synthetic strategy possessing high product yield, short reaction time, and convenient handling. The molecular docking results were found in good correlation with experimental IC₅₀ values.

The increasing global health problem of bacterial resistance to the major classes of antibiotics is driving scientists to search for newer antimicrobial agents. The present work was designed to synthesize and evaluate the antimicrobial activities of a new series of sparfloxacin derivatives. Aseries of 22 new sparfloxacin derivatives (1 – 22) were synthesized followed by their spectral characterization and antimicrobial evaluation using serial dilution method. QSAR studies were performed to relate their antimicrobial activity and structure. The results of antimicrobial activity testing against all the three selected bacterial strains (Bacillus subtilis, Staphylococcus aureus, and Escherichia coli) indicated that compounds 21 and 22 exhibited maximum antibacterial potential among all the synthesized sparfloxacin derivatives. Compounds 6, 17, and 22 exhibited maximum antifungal potential against two fungal strains (Candida albicans and Aspergillus niger). The results of QSAR studies revealed the fact that topological parameters, particularly the valence third-order molecular connectivity index, are the major factor in influencing the antibacterial potential of the synthesized molecules. These new derivatives can offer new avenues in the design of better antimicrobial molecules active against drug-resistant bacterial and fungal strains.

The influence of the isomalt mass fraction in a mixture with glucose on the flowability, density, and elastic-plastic properties of the tableting mass and the quality of the obtained 1-g tablets (14 mm diameter) was studied. The flowability of the mixture decreased by 0.6 ± 0.06 g/c if the isomalt ST-PF content was increased by 10%. The curve for the bulk density had a distinct maximum near an isomalt–glucose ratio of 50:50. The tablet strength increased linearly by 55 ± 7 and 51 ± 7 N; the density, by 0.0036 ± 0.0002 and 0.076 ± 0.003 g/cm³; and the disintegration time, by 1.2 ± 0.2 and 1.7 ± 02 min if the isomalt ST-PF concentration in the mixture was increased to 35% and the compaction pressure to 350 N/cm², respectively.

The purpose of this work was to develop a sensitive and validated HPLC method for analysis of rivaroxaban and estimation of related impurities in parent drug substance and pharmaceutical dosage forms. The analysis was carried out on a Macherey-Nagel Nucleodur C18 column (250 × 4.6 mm, 5 μm particle size) with a mobile phase containing acetonitrile and water in gradient program at a flow rate of 1.5 mL/min, the column oven temperature 55°C, and the UV detector wavelength set at 254 nm. The method was validated according to USP38-NF33 guideline recommendations and to the ICH guidelines for validation. The linearity, selectivity, accuracy, precision, robustness, LOD and LOQ characteristics of the proposed method showed acceptable values. The method is suitable for practical routine analysis of drug substance and pharmaceutical dosage forms, and it was successfully used to analyze Rovaltro (Syrian product) and Xarelto (brand product). All the analysis results were acceptable according to pharmaceutical requirements.

Amethod for quantitative determination of total saponins in Aralia elata (Miq.) Seem. (A. mandshurica Rupr. et Maxim.) roots was developed using spectrophotometry at 510 nm of products from the reaction of the analytes with conc. H₂SO₄ as recalculated for saparal (total ammonium salts of aralia saponins) or the average specific absorption coefficient of saparal. The total saponin contents in the raw material varied from 9.41 ± 0.18 to 10.46 ± 0.15%. The error of a single determination using the developed method with confidence probability 95% was less than ± 1.43%.

The possibility of immobilizing benzocaine in polymeric nanocontainers made of sulfonated cation exchangers, i.e., sulfonated polycalixarene and KU-23 30/100, was studied. The desorption kinetics of neutral and cationic benzocaine from the polymeric nanocontainers provided the desired drug-release pharmacokinetics upon peroral administration.

A gas-chromatographic method for quantitative determination of phenol in biological drugs was developed. The optimal chromatography conditions were a DB-WAX column (30 m × 0.25 mm × 0.25 μm, Agilent Technologies); injector temperature 250°C; split ratio 40:1; sample volume 0.5 μL; He carrier gas; constant pressure mode; flow rate 1.4 mL/min; furnace temperature profile: initial 160°C (constant for 3 min), ramp at 40°C/min to 200°C (constant for 0.6 min), ramp at 40°C/min to 220°C; analysis time 7.133 min; and detector temperature 250°C. The method was validated. The analytical range of the method was phenol concentrations from 1 to 5 mg/mL. The accuracy and specificity of the method were confirmed. The precision was evaluated. The results allowed this method to be considered an alternative for quantitative determination of phenol in biologicals.