Vol 51, No 7 (2017)

Simultaneous administration of a copolymer of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine and cytostatic agents to mice with a variety of implanted tumors was found to increase treatment efficacy, promoting increases in survival time. This effect is of interest for further studies of the possible use of copolymer as an immunomodulator in chemotherapy.

The randomized crossover (2 × 2) protocol is a standard design for studies of bioequivalence, reducing intraindividual variability. Determination of cohort size for studies of bioequivalence is an important element in planning studies and must be evidence-based. The aim of the present work was to produce and validate an algorithm for determining the required cohort size for studies of bioequivalence using computer simulation. The proposed algorithm is based on a procedure for assessing the power of the statistical test for known numbers of observations, variance, and preset values of acceptable first-order error levels.

Cyclocondensation of dialkylbenzylcarbinols with benzylcyanides was used to synthesize 1-benzyl-3,3-dialkyl-3,4-dihydroisoquinolines. The hydrochlorides of the compounds synthesized here were tested for antiarrhythmic activity in a calcium chloride model. The maximum antiarrhythmic index (AI) was found with isoquinolines with cycloalkanone fragments such as cyclopentanone and cyclohexanone in position 3, which had AI values of 15.5 and 16.3, three times the corresponding value for lidocaine.

Continuing the search for novel biologically active substances among the 4-hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxamides series, we report here the synthesis of a series of {[(4-hydroxy-1-methyl-2,2-dioxido-1H-2,1-benzothiazin-3-yl)carbonyl]amino} benzoic acids asd their derivatives at the carboxyl group. Pharmacological testing showed that compounds with a free carboxyl group are of interest as potential diuretics, while carbamide derivatives have potential as analgesics. Esterification of the carboxyl group with lower alkyl alcohols was less effective.

A series of 2-pyrazoline derivatives (PS-1 to PS-16) were synthesized by reacting different aromatic/heteroaromatic aldehydes and ketones, in a two-step reaction through Claisen – Schmidt condensation, followed by cyclization of the resulting chalcones with hydrazine hydrate in the presence of a base using conventional and microwave approaches. The synthesized derivatives were characterized by various physicochemical methods including IR, ¹H-NMR, ¹³C-NMR, and mass spectroscopic data and elemental analysis. The antidepressant and anti-anxiety activities were evaluated using suitable animal models. Compounds PS-3, and PS-14 showed noticeable antidepressant activity, by reducing the duration of immobility in both tests, while compounds PS-9 and PS-12 were found to possess good anxiolytic activity (by increasing the number of arm entries and open arm exploratory time) at the tested doses (50 and 100 mg/kg b.w.) in comparison to standard drugs imipramine and diazepam, respectively. In order to elucidate binding interactions of the synthesized derivatives to the MAO-A target protein, molecular docking was employed which demonstrated the key interactions with amino acid residues Phe208, Asn181, and Tyr407 at the binding site. Further, the ADME properties of the synthesized derivatives were predicted and found to fall within the stated limits.

A convenient protocol for the synthesis of coumarin appended 1,3-benzoxazine derivatives (4a – 4g) is described. Cyclisation of hydrazones (3a – 3g) using triphosgene in dichloromethane gave the corresponding 1,3-oxazines in a relatively good yield. The proposed structures of newly synthesized compounds were confirmed by spectral methods and elemental analysis. Oxazine derivatives 4a – 4g were evaluated for their in vitro antimicrobial activity against various bacteria and fungi. Compounds 4b and 4d inhibited growth of test microbes thus proving significant antimicrobial activity. In addition, in vitro antioxidant activity of the synthesized compounds was evaluated and compared to that of standards, showing DPPH, NO, and OH radical scavenging properties. Compounds 4b and 4f exhibited higher antioxidant activity than a standard drug.

This study demonstrated the antioxidant activity of aqueous and aqueous-ethanolic (40%, 70%, 95%) extracts of the above-ground parts of the dropwort (Filipendula vulgaris Moench) in relation to the process of electroreduction of oxygen. Antioxidant properties were more marked in the more lipophilic dropwort extract. The lipophilic fraction of the aqueous extract (extracted with ethyl acetate) had marked antioxidant activity, and its efficacy was greater than those of dihydroquercetin and ascorbic acid, and this resulted from the more complete extraction of total biologically active compounds of phenolic (simple phenols, flavonoids, hydroxycoumarins, phenolcarboxylic acids) and triterpene (acids, saponins) nature, as well as amino acids.

Solubilization of rifapentine with human serum albumin (HSA) was used to produce a water-miscible form consisting of a colloidal suspension of particles of size 538 ± 9 nm. Dilution of the suspension more than 20-fold led to dissociation of the aggregates formed during solubilization procedure, producing a transparent solution. This was associated with a reduction in particle size to 10 – 20 nm, corresponding to the particle size in HSA solution at the same concentration. A fluorescence method showed that suspensions contained both free rifapentine and its complex with HSA. Studies of the activity against the pathogen of tuberculosis, Mycobacterium tuberculosis H37Rv, in a model of acute infection in Balb/c mice showed that the water-miscible form of rifapentine given intravenously had high activity against mycobacteria, comparable with the activity of rifapentine substance, decreasing mycobacterial loadings in the parenchymatous organs from 10⁶ – 10⁷ to 10² – 10³ cfu/organ. Thus, use of HSA as solubilizer yielded an intravenous form of rifapentine retaining the activity of the antibiotic against Mycobacterium tuberculosis.

Thiazolo[2, 3-f]purine derivatives and their analogs – dihydrothiazolo[2, 3-f]purine, 7-(thietan-3-yl)purine, and 8-(2-hydroxypropylthio)purine derivatives – were synthesized. The compounds synthesized here had no effects on protein glycation reactions using glucose; they gave weak inhibition of glycogen phosphorylase; they had no hemorheological activity. Substances with hypotensive activity greater than that of Dibazol were found. A number of substances had hypoglycemic effects greater than those of chlorpropamide and Adebit. Two compounds inhibited dipeptidylpeptidase-4, but were less active than reference agent vildagliptin.

The alkaloid from the yellow waterlily nuflein, whose preparation is described here, has cytotoxic activity against HeLa cervical cancer tumor cells. Suppression of the viability of normal fibroblasts requires nuflein concentrations 67 times greater than suppression of the viability of the same number of HeLa tumor cells. Cytotoxic activity is mediated by induction of the mitochondrial apoptosis pathway, as nuflein induces opening of mitochondrial pores and release of cytochrome c, which activates caspases. Nuflein also inhibits cellular energy generation due to uncoupling of oxidative phosphorylation in mitochondria and inhibition of mitochondrial respiration. The cytotoxic action of nuflein has been suggested to result from the properties of the sulfur atom in the thioether bond in the pharmacophore molecule. Utilization of the chemical properties of nuflein, allowing its steric structure to be “tuned,” may lead to the creation of a whole series of probes with different activities directed at modifying or inhibiting biologically important thiols. The greater selectivity of the antiproliferative activity of nuflein in relation to tumor cells as compared with the known antitumor substance cisplatin points to a specific antitumor nature for the activity of nuflein.

An effective method of dehydrating 9_-hydroxyandrost-4-ene-3,17-dione by mineral acids in organic solvents, producing essentially quantitative formation of androsta-4,9(11)-diene-3,17-dione is proposed. Quantitative isomerization of the side product androsta-4,8(9)-diene-3,17-dione to target product was shown to be pssible.

We report here the selection and evidential basis of optimum conditions for the chromatography of glutamic acid in a thin layer of sorbent. The conditions for identifying and assaying this amino acid by high-performance thin layer chromatography on a personal computer using specialist software were optimized. The method was used to estimate glutamic acid contents in complexes of free amino acids in extracts from medicinal herb material (using sea buckthorne fruits and nettle leaves as examples).

In this work, Ce³⁺doped clindamycin nanoparticles (Ce³⁺/CLA-NP) loaded in gelatin media were prepared by sol-gel technique and characterized by x-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and photoluminescence (PL) spectra. The PL spectra of Ce³⁺/CLA-NP show two UV bands, at 325 and 355 nm, which are not detected from undoped CLA-NP. The morphology of the nanocomposite and the size of nanoparticles were estimated by scanning electron microscopy (SEM). The average particle size in Ce³⁺/CLA-NP was about 50 – 120 nm. The drug release profile was determined by UV–Vis spectroscopy. Finally, in vitro antibacterial properties of Ce³⁺/CLA-NP were evaluated against Staphylococcus aureus.