Anatomical study and histochemical analysis of Artemisia leucodes Schrenk.

The study of anatomical structure of the aerial part of Artemisia leucodes Schrenk. was carried out, and in this regard, the anatomical and diagnostic features of A. leucodes raw materials were revealed: epidermal cells of an elongated shape, mesophyll in the leaves is columnar, the stem has a fascicular structure, collenchymal mechanical structures are present in the stem ribs. Histochemical analysis shows that the secretory structures of A. leucodes produce sesquiterpene lactones and essential oils, as was confirmed by a chemical study of the aerial parts of A. leucodes. Sesquiterpene lactones anhydroaustricin, matricarin, leucomisin, grossmizin, 5ß(H)-austricin, were isolated from the ethanol extract of A. leucodes by column chromatography on silica gel. By hydrodistillation of anthodium, buds, and leaves an essential oil was obtained, according to chromatography-mass spectrometry, the major component of which was l-camphor - 39.00% and camphene - 9.31%, 1.8-cineole (eucalyptole) - 6.20%. The obtained data on diagnostic features, determination of the localization of secondary metabolites and chemical composition allow us to identify and standardize the medicinal raw materials of A. leucodes, what guarantees quality, and also allow more rational use of A. leucodes in pharmaceutical production.

Experimental, Clinical and Morphological Analysis of H-Ras Oncoproteins for Locally Advanced Breast Cancer.

BACKGROUND: Activated forms of Ras are enhanced in both breast cancer as well as the cell lines with EGFR and HER2 expression. Therefore, H-Ras could be activated in breast tumours in the absence of direct mutational activation of Ras itself and could contribute to 20-50% of the cases. Expression inhibition, signal transduction interruption from H-Ras to the nucleus could become a promising therapeutic target. AIM: The aim of this study was to investigate the clinical and morphological criteria of locally advanced breast cancer and the expression of H-Ras oncoprotein in patients who have been subjected to different regimens of farnesyltransferase inhibitor. METHODS: H-Ras status was assessed by immunohistochemistry (IHC). RESULTS: An association between the expressions of H-Ras and Her2/neu (p = 0.001) as well as the tumour proliferation index Ki-67 (p = 0.001) in patients with breast cancer was established. Analysis of the relationship between H-Ras expression showed a relatively strong association with progression-free survival both before the treatment (V = 0.47; p = 0.001) and after the treatment (V = 0.45; p = 0.001). These results may indicate the clinical applicability of H-Ras as a prognostic factor or serve as a therapeutic target for breast cancer treatment. CONCLUSION: These results could indicate the potential clinical application of H-Ras as a prognostic factor or a therapeutic target for breast cancer treatment.

Sesquiterpene lactones with unusual structure. Their biogenesis and biological activity.

The given review provides data on the new sesquiterpene lactones with unusual structure isolated from various natural sources, e.g. fungi, plants, marine growth; about their spread, biological activity, and the presumed biogenetic pathway of their formation. An attempt was made to biologically justify a wide structural formation variety of new sesquiterpene lactones with the unique structure.

Chemical modification of arglabin and biological activity of its new derivatives.

This review summarizes the results of own research on chemical modification of the molecule of sesquiterpene lactone arglabin from Artemisia glabella Kar. et Kir. Over 70 new arglabin derivatives were obtained which are polyfunctional compounds with oxy functions, atoms of haloids, phosphorus, nitrogen, and cyclopropane fragments. For the first time the results of bioscreening of new arglabin derivatives are reported.

[Experimental study of pinostrobine oxime biotransformation].

We have experimentally studied pathways of elimination of an oximized derivative of phytoflavonoid pinostrobine by HPLC/mass spectrometry. Four potential metabolites of pinostrobine oxime have been found and there was an attempt to determine their molecular structures on the basis of their fragmentation under positive electrospray ionization conditions. It is established that pinostrobine oxime is removed from the organism mainly unchanged and also in the form of glucuronated derivative.

[Experimental evaluation of the antibacterial and phagocytosis-stimulating properties of leucomisine].

It is experimentally demonstrated that the sesquiterpene lactone leucomisine extracted from Artemisia leucodes exhibits pronounced antibacterial and phagocytosis-stimulating activity.

[Effect of leucomisine on cell and humoral immunity indices].

The influence of the sesquiterpene lactone leucomisine on the cell and humoral immunity indices has been studied. It is established that the administration of leucomisine in a dose of 10 mg/kg dose stimulates IgM and IgG antibody production.

[Features of leucomisin pharmacokinetics in the blood serum upon introduction by various methods].

Pharmacokinetics of the sesquiterpene lactone leucomisin in the blood serum was studied after single intraperitoneal injection and enteral introduction. Analysis of the main pharmacokinetic prameters shows that the drug circulates in the organism for a relatively long time and can be accumulated in the cells, probably, due to the ability of penetrating through the histohematic barriers.

[Anti-inflammatory effect of arglabin and 11,13-dihydro-13-dimethylaminoarglabin hydrochloride]. / Protivovospalitel'nye svoistva arglabina i gidrokhlorida 11,13-digidro-13-dimetilaminoarglabina.

The sesquiterpene lactone arglabin, as well as its derivative 11,13-Dihydro-13-dimethylaminoarglabin hydrochloride, exhibit antiexudative and antiproliferative properties on the models of acute aseptic inflammation caused by formalin, carrageenan, and histamine, and on the model of proliferative inflammation accompanying cotton-pellet granuloma.

Arglabin-DMA, a plant derived sesquiterpene, inhibits farnesyltransferase.

Arglabin [1(R),10(S)-epoxy-5(S),5(S),7(S)-guaia-3(4),11(13)-dien-6, 12-olide], a sesquiterpene gamma-lactone is isolated from Artemisia glabella, a species of wormwood endemic to the Karaganda region of Kazakstan. The compound has been modified to render it water-soluble through addition of a dimethylaminohydrochloride group to the C(13) carbohydride moiety to yield Arglabin-DMA. Arglabin-DMA is a registered antitumor substance in the Republic of Kazakstan. Previously, we have shown that this compound prevents protein farnesylation without altering geranylgeranylation. We now report that Arglabin-DMA inhibits the incorporation of [(3)H]farnesylpyrophosphate into human H-ras protein by FTase with an IC(50) of no greater than 25 microM. Kinetic studies show that the phosphorylated form of this compound competitively inhibits the binding of farnesyl diphosphate to FTase. This mechanism of action is different from other reported peptidomimetic FTIs which lower the affinity of ras protein to FTase. Our in vitro studies confirm that Arglabin-DMA inhibits post-translational modification of ras protein in cells. Arglabin-DMA inhibits anchorage-dependent proliferation of NB cells (IC50=10 microg/ml) and inhibits anchorage-independent growth of NB and KNRK cells with about the same IC(50). Soft-agar colony formation assay of H-ras and K-ras transformed cells show IC(50)s to be 2 and 5 microg/ml, respectively. In primary cultures of human tumor cells, Arglabin-DMA inhibits cell proliferation of a variety of tumor types with IC(90)s in the range of 0.85 to 5.0 microg/ml. Because of these pharmacologic properties, we propose that Arglabin-DMA is suitable for the treatment of ras related malignancies.

[Genetic control of the biotransformation of plant terpenoids by Pseudomonas strain SP.1K1]. / Geneticheskii kontrol' biotransformatsii terpenoidov rastitel'nogo proiskhozhdeniia s pomoshch'iu shtamma Pseudomonas SP.1K1.

Bacterial strain Pseudomonas sp. 1K1 can grow on sesquiterpene lactones isolated from medicinal plants of Kazakhstan due to 18-kb conjugative plasmid. This plasmid is stable in heterologous environment (E. coli and B. subtilis), which was proven by transformation transfer. The possibility of using salicylate as p1K1 selective agent has been demonstrated.