S. M. Adekenov’s research while affiliated with Kazakhstan International School and other places

Herbal ingredients are widely used in practice due to their broad pharmacological effects and absence of side effects. However, despite their remarkable pharmacodynamic activity, most of the herbal ingredients have shown lower bioavailability in vivo conditions. New drug-delivery systems acquired vital importance because of higher bioavailability and overall therapeutic efficacy. A review of various studies on the production and application of phytosomal medical forms, which are in the form of hybrid molecules with high solubility in lipid and aqueous environments, is presented in this article. In an aquatic environment phytosomes group and form micelles. Phytosomes are used for increasing the bioavailability of the medical component, targeted delivery, and increasing the effect of the action of a medical drug while decreasing its therapeutic dose. Expanding the range of phytosomal medicinal forms, including sesquiterpene lactones, flavonoids, and other hydrophilic compounds is a perspective direction. In literary sources, methods for establishing quality control are practically absent and require development as well as unification.

The article presents the results of a chemical study of Rhaponticum carthamoides (Willd.) Iljin. and Rhaponticum serratuloides (Georgi.) Bobr., which are of interest as sources of new adaptogenic, anabolic, and antiparasitic drugs; a method for complex chemical processing of the raw materials of the above-mentioned plants has been proposed. The structure of new sesquiterpene lactones raposerine, raserolide, 15-deacetylraposerine, and raserine has been isolated and established. The content of pharmacologically active ecdysterone in various organs of the studied Rhaponticum species is discussed according to the phenological phases of plant development. The antiparasitic, antiviral activity and cytotoxicity of the isolated compounds were determined.

BACKGROUND: A supramolecular complex of ecdysterone triacetate with β-cyclodextrin (β-CD) was synthesized to obtain new potentially bioactive substances and study the effect of bulky pharmacophore-functional groups on the preservation of the specific activity of 20-hydroxyecdysone. The adaptogenic and anabolic activities of the resulting water-soluble inclusion complex were studied. It was established that with the introduction of 3 acyl-pharmacophore groups in the form of encapsulated and hydrophilic supramolecular forms to experimental animals at a dose of 10 mg/kg, the studied complex has anabolic and adaptogenic effects, including increased stress resistance, increased physical endurance, as well as slightly increased weight of the heart and gonads compared to the control. AIM: Study of the specific activity of the supramolecular complex of ecdysterone 3-acetate with β-CD. METHODS: During the experimental study of the adaptogenic and anabolic effects of the supramolecular complex of ecdysterone 3-acetate with β-CD, the “open field” and “free swimming” tests were used. Statistical processing of the results was carried out using the Statistica 8 software package. Intergroup differences were assessed using the non-parametric Mann–Whitney U-test. For unpaired related groups, the non-parametric Wilcoxon test was used. CONCLUSIONS: It has been established that physical activity (swimming) simultaneously has a significant stressor effect on animals and is characterized by an increased supply of glucose into the blood and the breakdown of blood proteins. It was revealed that the supramolecular complex of ecdysterone 3-acetate with β-CD at a dose of 10 mg/kg has anabolic and adaptogenic effects, in particular increased stress resistance and physical endurance of animals, as well as a slightly increased weight of the heart and gonads compared to the control.

Five cyclopentadienone sesquiterpene lactones: austricin, 5β(H)-austricin, achillin, grossmisin and leucomisin were obtained from the plant Artemisia leucodes Schrenk. The lactone purification procedure starting from the plant leaves is described. A quality control method was developed using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). For these stereoisomeric cyclopentadienone guaianolides, the TLC and HPLC relationships “molecular structure—retention time” on the nature of the substituent in the molecular structure were studied. The chromatographic conditions were optimized and the influence of the structure of the molecule on their retention time was discussed comparing retention in both TLC and HPLC methods. The relationship between the structure of a particular cyclopentadienone guaianolide and its chromatographic retention time characterizes the sorption mechanism with the apolar stationary phase. It gives information on the compound polarity and hydrophobicity, information most relevant for these biologically active sesquiterpene γ-lactones, which are possible potent active ingredients of drugs.

The article presents the results of the development of technology for isolating essential oil from the buds of Populus balsamifera L. and a medicinal substance based on it. For the first time, a technology has been developed for the quantitative isolation of essential oil from the buds of Populus balsamifera L. by the barothermal method at a temperature of 140 ºC, under a vacuum of 1333‒2000 Pa. The main components of the essential oil of Populus balsamifera L. buds, isolated by the barothermal method, were determined to be α-bisabolol, β-eudesmol, and 2-phenylethyl-2-methylbutanoate. A technological scheme for the production of essential oil substance from Populus balsamifera L. buds has been developed, including 2 stages of the main technological process and 2 stages of auxiliary work, and its pilot industrial regulations. The control points during the isolation and preparative production of the essential oil substance from the Populus balsamifera L. buds are the major components α-bisabolol and β-eudesmol. The main critical points in the production of a substance based on the essential oil of Populus balsamifera L. buds are pressure, temperature, and duration of isolation. The stages of production of the substance are controlled using a standard sample of α-bisabolol (1). A quantitative determination of 108 components of essential oil from Populus balsamifera L. buds was carried out, as well as standardization for organoleptic properties and major components. A comparative analysis of essential oil from Populus balsamifera L. buds collected in the vicinity of Karaganda and the North Kazakhstan region was carried out. A substance based on essential oil from Populus balsamifera L. buds has antimicrobial, wound-healing, and antitumor activities with relatively low toxicity.

The article discusses the results of 19 samples screening of sesquiterpene γ-lactones argolide, grosheimin, estafiatin, and their derivatives for cytotoxicity and antitumor activity. The research results indicate significant cytotoxicity and selectivity of the action of sesquiterpene γ-lactones and their derivatives against most tumor cell lines. Aim. The purpose of this study is to study the cytotoxicity and antitumor activity of the sesquiterpene γ-lactones argolide, grosheimin, estafiatin and their chemically modified derivatives, as practically renewable materials. Methods. The cytotoxicity of the compounds was determined using vero cells, THP-1, Pliss lymphosarcoma cell lines, Walker carcinosarcoma, sarcoma 45, sarcoma-180, alveolar liver cancer PC-1, P-388 leukemia, L-1210 leukemia, and resistant to 5-fluorouracil sarcoma 45. The antitumor activity of the samples was studied in in vivo experiments on white outbred rats with transplanted tumor strains and was assessed by inhibition of tumor growth and the magnitude of the increase in average life expectancy. Statistical processing of the results was carried out using the program “GraphPad Prism v. 6.0" (GraphPad Software Inc., USA). Conclusion. When determining cytotoxicity in in vitro samples of the sesquiterpene γ-lactones argolide, grosheimin, and estafiatin showed selectivity of their action on cells of 8 tumor lines, on cells of human acute monocytic leukemia THP-1 and in relation to the larvae of sea crustaceans Artemia salina (Leach). Samples of argolide, 8-acetylgrosheimin, 13-morpholinogrosheimin, 3-keto-4-methylene-cis-guaianolide, 3α-acetoxyisozaluzanin C, and 10α(14)-epoxy-1,5,7α,4,6β(H)-guai-11(13)-en-4(3),6(12)-diolide in experiments in vivo possessed high antitumor activity against transplantable tumor strains of Pliss lymphosarcoma, Walker carcinosarcoma, sarcoma 45, sarcoma 37, sarcoma 180, alveolar liver cancer PC-1, leukemia P-388 and L-1210, resistant to 5-fluorouracil sarcoma 45