Vol 49, No 10 (2016)

Flavonoids are a large group of polyphenolic compounds that are present in almost all higher plants. Recent research demonstrated a wide range of biological effects of these compounds under both normal and various pathological conditions. Apparently, the biological activity of most flavonoids is due mainly to their ability to penetrate into cells and block enzymes of signaling pathways and transcription factors, including those involved in the activation, proliferation, and realization of effector functions of immune system cells. Moreover, it should be noted that flavonoids were highly efficacious in several instances in experimental therapy of model immune pathologies, suggesting that they were promising as platforms for creating new pharmacological agents that suppress or “normalize” the immune response.

A series of phenyl- and alkylthiocarbamides were synthesized by the reaction of 2,9-disubstituted imidazo-[1,2-a]benzimidazoles with phenyl- and alkylisothiocyanates. The structures of the products were confirmed by elemental analysis and PMR spectroscopy. Some of the synthesized compounds were capable of inhibiting non-enzymatic glycosylation of proteins. The concentration dependences of the antiglycation effect of the most active substances and aminoguanidine were studied.

Ethyl-2-amino-1-benzamido-4-oxo-5-(2-oxo-2-arylethylidene)pyrrolidine-3-carboxylates (IIa-g) were synthesized via recyclization of 3-(2-benzoylhydrazono)-5-arylfuran-2(3H)-ones (I) through the action of ethylcyanoacetate. The synthesized compounds were screened for biological activity and were found to have low toxicity. Ethyl-2-amino-1-benzamido-5-[2-(3, 4-dimethoxyphenyl)-2-oxoethylidene]-4-oxopyrrolidine-3-carboxylate exhibited antiradical activity in a diphenylpicrylhydrazyl (DPPH)-binding assay that was greater than that of the reference drug trolox. This same compound showed anti-inflammatory activity in a carrageenan edema model that was greater than that of diclofenac sodium. Assessment of antihypoxic activity in an acute normobaric hypoxia test found that ethyl-2-amino-1-benzamido-5-[2-oxo-2-(4-methylphenyl) ethylidene]-4-oxopyrrolidine-3-carboxylate was comparable with the succinic acid standard.

The reaction in aqueous medium of phytic acid (myo-inositol hexakisphosphate) and glucosamine hydrochloride (2-amino-2-deoxy-β-D-glucopyranose hydrochloride) formed phytic acid—glucosamine complexes of formula InsP₆ 5GA. Their compositions were proved by elemental analysis for C, H, N, and P. IR, PMR, ¹³C NMR, and ³¹P NMR spectroscopy and potentiometric titration showed that the complexes of phytic acid and glucosamine were formed by H-bonds and electrostatic salt interactions. High antioxidant activity against lipid peroxidation and a positive effect on superoxide dismutase activity were found for complexes of InsP₆H₁₂ and glucosamine in in vitro studies of human blood plasma under oxidative stress.

A series of ethyl-1-(4-aminosulfonylphenyl)-5-aryl-3-hydroxy-2-oxo-3-pyrroline-4-carboxylates were synthesized via a three-component reaction of sodium diethyloxalylacetate and a mixture of an aromatic aldehyde and 4-aminobenzenesulfonamide. The structures of the compounds were established using IR and PMR spectroscopy and mass spectrometry. The antibacterial and immunobiological activities of the synthesized compounds were studied.

New highly active N¹-substituted uracil derivatives of the HIV-1 nonnucleoside reverse transcriptase inhibitor class were designed. The structure—activity relationship provided a basis for building a computer model of the inhibitory activity against reverse transcriptase of HIV-1 mutant K103N/Y181C. New compounds that were more active than nevirapine were synthesized.

Despite advances in anticancer drug development and discovery, the survival of patients is so poor. A deep need for discovery of novel anticancer drugs is among priority issues in medicinal chemistry now. A new series of 1,2,4-triazole derivatives were designed and synthesized by means of bioisosteric replacement. In vitro cytotoxicity evaluation was carried out with respect to PC3 (prostate carcinoma), HT29 (colorectal cancer) and SKNMC (neuroblastoma) cell lines using MTT assay, and the obtained results were compared to imatinib as a reference drug. Spectroscopic methods including 1H NMR, IR, and MS were used for characterization of the synthesized compounds. Generally, none of the tested compounds showed superior activity in comparison to imatinib against PC3 and SKNMC cell lines. However, compound 3b (IC₅₀ = 3.69 ± 0.9 μM) and 3e(IC₅₀ = 15.31 ± 2.1 μM) exhibited higher activity than imatinib (18.1 ± 2.6) against HT29 cells. Some of the obtained 1,2,4-triazole derivatives can be proposed as potential anticancer agents – in particular, against colorectal cancer – but further structural modifications and experimental tests are needed to increase the anticancer activity.

Solutions containing pharmaceuticals of various origins are one of the most popular dosage forms. Pharmaceuticals for parenteral, ophthalmic, internal, and external use, among others, are prepared as solutions. However, a general monograph for the Solutions dosage form has not yet appeared in the Russian State Pharmacopoeia. The principal regulations, including relevant monographs of leading global pharmacopoeias, for the quality requirements of the Solutions dosage form were analyzed and enabled a list of the principal quality parameters of solutions, the techniques and methods for their determination, and the normalized ranges that would be used subsequently to compose a general pharmacopoeial monograph Solutions to be compiled.

Microcrystals of 6α-methyl-16α,17α-cyclohexapregn-4-ene-3,20-dione (mecigestone) that differed from the starting drug substance by decreased sizes and altered morphologies were produced using a Nano Spray Dryer B-90 (Buchi, Switzerland) that allowed operation with organic solvents in a closed cycle. The bioavailability of starting crystalline and micronized mecigestone drug substance was studied by oral administration to laboratory white rats. Mecigestone was extracted from rat blood serum using solvent extraction. The extraction coefficient was 64%. The detection limit of the drug substance was 0.08 ng/mL. The content of unaltered mecigestone in the extracts was determined using HPLC with high-resolution mass spectrometric detection. Micronized mecigestone was 7.5 times more bioavailable than the starting drug substance.

Mixed-valence Ir–Ru oxides (IrO_x—RuO_x) electrodeposited on a glassy-carbon electrode surface were found to exhibit catalytic activity for caffeine oxidation. An amperometric method for caffeine detection at this modified electrode under batch-injection analysis conditions was developed. The analytical signal was linearly dependent on the caffeine concentration in the range 5 × 10⁻⁸ – 5 × 10⁻³ M. The developed method was tested for caffeine determination in tablets, solutions for injection of caffeine—sodium benzoate, and coffetamin tablets.