Vol 51, No 6 (2017)

Non-enzymatic interaction of reducing sugars with free amines of proteins (Maillard reaction) leads to the formation of advanced glycation end products (AGEs) and is an important factor in the pathogenesis of diseases such as atherosclerosis, heart failure, inflammation, rheumatoid arthritis, and neurodegenerative disorders. AGE formation is especially prevalent with hyperglycemia and underlies the pathogenesis of microvascular and macrovascular complications of diabetes mellitus (DM). This review covers the main steps of the Maillard reaction, the pathophysiological role of its products in the development of DM complications, possible ways of pharmacological correction of the process, and the main protein-glycation inhibitors known today.

A method for separating a mixture of calf brain peptides by extraction with aqueous HOAc followed by fractionation of the extract by cross-flow (tangential) microfiltration and solid-phase extraction was developed. The isolated peptide mixture contained constituents with molecular masses within 0.1 – 3 kDa. Low-pressure ion-exchange chromatography of this mixture over Dowex 50WX8 sulfonated cation exchanger isolated a pure peptide consisting of the five amino acids Arg, Lys, Gly, Ser, and Leu. The biological activity of the obtained pentapeptide was estimated on organotypic brain slice culture explants of Wistar rats. It was established that the peptide possessed high tissue-specific and stimulatory activity for brain explants that was greater than those of the commercial preparations Cortexin and Cerebrolysin.

Methods for synthesizing new heterocyclic compounds based on 1,3,4-thiadiazoles were developed. It was shown that these compounds possessed pronounced antifungal activity and could be recommended for further investigation as potential antimicrobial agents with fungicidal activity.

Results from toxicological and pharmacological studies of the iron(II) coordination complex of the immunoactive dipeptide isoleucyltryptophan (timofer) were presented. It was established that timofer was practically nontoxic and exhibited high immunostimulatory activity when combined with viral and bacterial vaccines.

Echinacea purpurea has been reported as a source of bioactive compounds and essential elements. Cichoric acid is a caffeic acid derivative known as appropriate marker for the quality of E. purpurea containing products. We have developed an efficient method of ultrasound-assisted extraction (UAE) of cichoric acid from roots of E. purpurea and optimized the process parameters. Comparison of the UAE and maceration techniques for the extraction of cichoric acid from of E. purpurea root was carried out. The concentration of cichoric acid in extracts was analyzed by high-performance liquid chromatography (HPLC). The optimum extraction parameters are 50% (v/v) ethanol – water mixture as solvent, sonication time of 10 min, solute to solvent ratio of 1/10, and extraction temperature of 30°C. The advantageous effect of ultrasonic waves on extraction of cichoric acid in comparison to maceration technique is established.

Methyl-4-hydroxy-1-phenyl-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylate was found to undergo transesterification even during crystallization from EtOH to convert into the corresponding ethyl ester. The molecular structure of the obtained compound was studied. In particular, PMR spectroscopy and x-ray crystal structure analysis established that the 1-N-phenyl substituent was situated in solution at an angle of ~60° to the plane formed by the aminophenylcarbinol fragment of the 2,1-benzothiazine whereas this angle increased to 80° in the crystal because of packing effects.

Insoluble camptothecin was converted into the corresponding hydrosoluble analog, camptothecin carboxylate, by using 1,1,3,3-tetramethylguanidine as hydrolyzing agent. The ethanol/K₂CO₃/H₂O aqueous two-phase system was established to extract the hydrosoluble camptothecin carboxylate. Through two-stage extraction from crude camptothecin of 5.4%, purity, final hydrosoluble camptothecin was obtained with a purity of 98.5% at a total yield of 78.4%.

A new rapid and accurate method for determining the mycophenolic acid concentration in human blood plasma using HPLC with tandem mass-spectrometric detection (HPLC-MS/MS) and deproteinization for sample preparation was developed. The method was validated according to the Guideline for Validation of Bioanalytical Methods of EMEA and Guidelines for Examination of Drugs. This method was used to study the pharmacokinetics of mycophenolate sodium.

To decrease the consumption of expensive active pharmaceutical ingredients (APIs) during the determination of their solubility limits by traditional classical methods, which are used in most of quality control laboratories over the world, an instrumental method has been developed based on the UV spectrophotometry. This study was focused on two types of pharmaceutical compounds. First, glatiramer acetate (GLA), also known as copaxone that is currently used to treat multiple sclerosis, has been studied as a water-soluble drug. Second, bortezomib (BZB), also known as velcade, which is an antineoplastic agent used for treatment of mantle cell lymphoma (cancer of the lymph nodes), as an organic-solvent (methanol) soluble drug. The results obtained by the proposed method are discussed and validated according to the solubility limits defined according to USP. Different batches of drugs were used to confirm that the results are reliable. Determination of the solubility of samples with unknown concentrations by using the constructed calibration curves showed that the solubility limit of GLA in water and BZB in methanol is defined as SOLUBLE and SPARINGLY SOLUBLE, respectively, which agrees with results of the traditional method.

Chinese white olive (Canarium album L.) is indigenous to the southeast area of China. Its fruits have been used as both food and folk medicine in China. Diversified economy values make this plant extensively cultivated to east-south China and other countries such as Vietnam, Malaysia, and Japan. The aim of the present article is to review nutritional ingredients and phytochemical constituents of Chinese white olive, recommend some fractions and monomers for the food industry and pharmacy, and have a look at the future prospects of this plant and its products. It is expected that Chinese white olive will help more people to stay healthy and gain financial strength.

A kilogram-scale synthesis of fingolimod drug substance was developed using a 30-L pilot setup. The target product was obtained by a four-step procedure in 99.8% purity and 47% overall yield.

The interchangeability of coagulation methods for determining the activity of recombinant blood clotting factor rFVIIa was assessed. Single-factor analysis of variance (ANOVA) and comparison of the metrological characteristics of the methods led to the conclusion that results obtained by reproducing the methods of the European Pharmacopoeia and Generium were comparable and interchangeable. One method could be used to confirm that a drug conformed to regulations established using another method. The Generium method was chosen for introduction into national pharmacopoeial practice because it was more economical.