44 research outputs found
Natural Sesquiterpene Lactones as Renewable Chemical Materials for New Medicinal Products
Literature data and own research results on the technology for isolating natural sesquiterpene lactones such as arglabin, alantolactone, artemisinin, grosheimin, isoalantolactone, parthenolide, santonin and potential possibilities of their use as renewable material for obtaining new compounds as well as biologically active derivatives are generalized in this review. Sesquiterpene lactones from plants are promising sources for the development and practical application of new original medical products possessing antitumor, anti-inflammatory, antimalarial, antiulcer, antiviral and immune-stimulating action. The technology for isolating sesquiterpene lactones is based on the extraction of raw plant material by different organic solvents with the subsequent chromatographic purification. The effective and environmentally safe technology for isolation and purification of sesquiterpene lactone arglabin from Artemisia glabella Kar. et Kir. by the Π‘Π2-extraction method is developed. Thereat, it was experimentally determined that the method for isolating arglabin from CO2 extract of Artemisia glabella Kar. et Kir. using centrifugal partition chromatography is effective for preparative isolation of the active substance and its manufacturing application. It is practically important to obtain water-soluble derivatives of biologically active sesquiterpene lactones and also to use the nanotechnology achievements for directed transportation of a molecule of the medicine in the human body thereby reducing toxicity of an active component. Promising direction is chemical modification of molecules in sesquiterpene lactones which are renewable material for obtaining new derivatives, thanks to which it becomes possible to solve two problems at the same time. Firstly, these researches help to obtain derivatives with higher biological activity or improved physical and chemical properties. Secondly, these researches enable us to disclose the mechanism of action of different medicines within the framework of βstructure-activityβ correlation. The article presents the literature data and own results on chemical modification of sesquiterpene lactones of alantolactone, arglabin, artemisinin, grosheimin, isoalantolactone, parthenolide and santonin. Various reactions on functional groups of these molecules were used to obtain a number of new derivatives of sesquiterpene lactones containing haloid-, pyrazole-, triazole-, amino-, dialkylamino-, hydroxy-, dialkyl phosphonate- and cyclopropane groups, which have shown high physiological activity
Heteroatom-Containing Natural Sesquiterpene Lactones and Methods for their Obtaining
This review shows the data about isolated heteroatom-containing sesquiterpene lactones from various genera of Asteraceae family, natural occurence, isolation methods and their biological activity. Chlorinecontaining sesquiterpene lactones were isolated from genera of Artemisia L., Achillea L., Acroptilon
Cass, Centaurea L., Chartolepis Cass, Eupatorium L., Jurinea Cass, Rhaponticum Adams, Saussurea DC. The greatest quantity of chlorine-containing sesquiterpene lactones were isolated from Centaurea genus. 25 new sesquiterpene lactones with chlorine atom in molecule were isolated and characterized. The sesquiterpene lactones, which in their structure contained a sulphur atom as a component of various alkoxyl-, thiohydroxygroups and acid residues, were isolated from genera of Eupatorium L., Petasites Mill, Helenium L., Acritopappus R.M. King and H. Rob., Arctium L., Saussurea DC. Nitrogen atom in the structure of natural sesquiterpene lactones is present in the form of amino groups as a part of ester groups as well as amino acids as Michael adducts. Nitrogen-containing sesquiterpene lactones were isolated from Acanthospermum Schrank, Saussurea DC. Isolated heteroatom-containing sesquiterpene lactones possess bactericidal, antifungal, cytotoxic, antiviral, virucidal, antiulcer and others activities. Another method for obtaining heteroatom-containing sesquiterpene lactones is a directed synthesis of chlorine-, fluorine-, bromine-, sulphur- and nitrogen-containing sesquiterpene lactones. On the basis of sesquiterpene lactone artemisinin known as an effective antimalarial preparation, we synthesized over 200 derivatives, among which fluorine-, chlorine-, bromine-, nitrogen-, sulphur- and azide-containing derivatives of artemisinin were obtained
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
Synthetic Derivatives of Natural Alkaloid Harmine
The indole alkaloid harmine was extracted from underground part ofΒ Peganum harmala L.Β With the purpose of obtaining the new biological active derivatives on base of alkaloid harmine the chemical modification was carried out. The p-toluolsulfochlorid, p-toluolsulfoacid, hydrochloric, sulfuric, nitric acids, dioxide selenium and phthalic anhydride have been chosen as modifiers. For the first time quaternary ammonium salts, derivatives of N-oxide and N (2)-oxyharminiumphthalate harmine are synthesized. The structure of the synthesized compounds is determined by methods of the spectral analysis and X-ray analysis. Antimicrobic and phagocytosis stimulating activities of isolated alkaloids and their derivatives are investigated
Comparative morphological and anatomical characteristics of Saussurea amara (L.) DC. and S. salsa pall. Spreng
In this paper, the authors conducted research of the comparative morphological and anatomical characteristics of two species of Saussurea, which grow in the steppes of Central Kazakhstan - S. amara L. (S. bitter) and S. salsa Pall. Spreng. (S. solonchak). Researchers revealed a number of clear distinctive morphological and anatomical signs of the over ground organs of S. amara and S. salsa, which make it possible to distinguish these species both as at the stage of collection of plants and also in the process of laboratory examination of the raw materials. The distinctive features of the anatomical stems of S. amara and S. salsa are the degree of furrows, strongly marked sclerenchyma of the conducting beams, and the size of parenchymatous cells of the primary cortex and the core. S. amara compared with S. salsa is characterized by more furrowed stems, less sclerenchyma in the conducting vascular bundles and smaller parenchymatous cells
Π‘ΠΠΠ’ΠΠ ΠΠΠΠΠΠΠ ΠΠΠΠΠΠΠΠ«Π₯ ΠΠ£ΠΠΠΠΠΠ
Ritterβs reaction of pulegone with a number of both aliphatic and aromatic nitriles in the presence of catalytic amount of concentrated sulfuric acid proceeding through formation of a tertiary carbocation with the subsequent addition of nitrile molecule and formation of ketoamides, has been performed.ΠΡΡΡΠ΅ΡΡΠ²Π»Π΅Π½Π° ΡΠ΅Π°ΠΊΡΠΈΡ Π ΠΈΡΡΠ΅ΡΠ° ΠΏΡΠ»Π΅Π³ΠΎΠ½Π° Ρ ΡΡΠ΄ΠΎΠΌ ΠΊΠ°ΠΊ Π°Π»ΠΈΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
, ΡΠ°ΠΊ ΠΈ Π°ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π½ΠΈΡΡΠΈΠ»ΠΎΠ² Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΠΊΠ°ΡΠ°Π»ΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΠ΅ΡΠ½ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΡ, ΠΊΠΎΡΠΎΡΠ°Ρ ΠΏΡΠΎΡΠ΅ΠΊΠ°Π΅Ρ ΡΠ΅ΡΠ΅Π· ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΠ΅ΡΠΈΡΠ½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠ±ΠΎΠΊΠ°ΡΠΈΠΎΠ½Π° Ρ ΠΏΠΎΡΠ»Π΅Π΄ΡΡΡΠΈΠΌ ΠΏΡΠΈΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ΠΌ ΠΊ Π½Π΅ΠΌΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ»Ρ Π½ΠΈΡΡΠΈΠ»Π° ΠΈ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΊΠ΅ΡΠΎΠ°ΠΌΠΈΠ΄Π°.
ΠΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎΠ΅ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΡΠΈΡΡΠ΅ΠΌΠ½ΠΎΠΉ Π±ΠΈΠΎΠ΄ΠΎΡΡΡΠΏΠ½ΠΎΡΡΠΈ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° Β«ΠΠ°ΡΠΌΠΈΠ½Π° Π³ΠΈΠ΄ΡΠΎΡ Π»ΠΎΡΠΈΠ΄, ΠΊΠ°ΠΏΡΡΠ»ΡΒ» Π² ΡΡΠ°Π²Π½Π΅Π½ΠΈΠΈ Ρ Π½Π°ΡΠΈΠ²Π½ΡΠΌ Π³Π°ΡΠΌΠΈΠ½ΠΎΠΌ Π½Π° ΠΊΡΠΎΠ»ΠΈΠΊΠ°Ρ ΠΏΠΎΡΠΎΠ΄Ρ Π¨ΠΈΠ½ΡΠΈΠ»Π»Π°
An experimental comparative study of the relative bioavailability of plant alkaloid harmine (native, in the form of a base) in comparison with its derivative harmine hydrochloride was carried out on chinchilla rabbit. Both substances was administered in capsules, containing an equimolar amount of harmine (50 mg, p.o.). Harmin hydrochloride was shown to have some pharmacokinetic advantages in comparison with native harmin due to a relatively rapid achievement of the maximal plasma concentration (Tmax) and a significantly higher maximum concentration of the active substance in the blood. At the same time, there was shown that the chemical modification of harmine does not significantly affect on such pharmacokinetics parameter as the area under the curve (AUC), which indicates the absence of a difference in the degree of absorption in the compared dosage forms.Π ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ΅ Π½Π° 12 ΠΊΡΠΎΠ»ΠΈΠΊΠ°Ρ
-ΡΠ°ΠΌΡΠ°Ρ
ΠΏΠΎΡΠΎΠ΄Ρ Π¨ΠΈΠ½ΡΠΈΠ»Π»Π° ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΎ ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ Π±ΠΈΠΎΠ΄ΠΎΡΡΡΠΏΠ½ΠΎΡΡΠΈ ΠΏΡΠΈΡΠΎΠ΄Π½ΠΎΠ³ΠΎ Π°Π»ΠΊΠ°Π»ΠΎΠΈΠ΄Π° Π³Π°ΡΠΌΠΈΠ½Π° (Π½Π°ΡΠΈΠ²Π½ΠΎΠ³ΠΎ, Π² Π²ΠΈΠ΄Π΅ ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΡ) ΠΈ Π΅Π³ΠΎ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΠΎΠ³ΠΎ Π³Π°ΡΠΌΠΈΠ½Π° Π³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄Π°, ΠΊΠΎΡΠΎΡΡΠ΅ Π²Π²ΠΎΠ΄ΠΈΠ»ΠΈΡΡ ΠΏΠ΅ΡΠΎΡΠ°Π»ΡΠ½ΠΎ, Π² Π΄ΠΎΠ·Π΅ 50 ΠΌΠ³, Π² Π²ΠΈΠ΄Π΅ Π΄Π²ΡΡ
ΠΊΠ°ΠΏΡΡΠ», ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ
ΡΠΊΠ²ΠΈΠΌΠΎΠ»ΡΡΠ½ΠΎΠ΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ Π³Π°ΡΠΌΠΈΠ½Π° (25 ΠΌΠ³). ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π³Π°ΡΠΌΠΈΠ½Π° Π³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄ Π² ΡΡΠ°Π²Π½Π΅Π½ΠΈΠΈ Ρ Π½Π°ΡΠΈΠ²Π½ΡΠΌ Π³Π°ΡΠΌΠΈΠ½ΠΎΠΌ ΠΎΠ±Π»Π°Π΄Π°Π΅Ρ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠΊΠΈΠ½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΏΡΠ΅ΠΈΠΌΡΡΠ΅ΡΡΠ²Π°ΠΌΠΈ Π² Π²ΠΈΠ΄Π΅ ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎ Π±ΡΡΡΡΠΎΠ³ΠΎ Π΄ΠΎΡΡΠΈΠΆΠ΅Π½ΠΈΡ ΠΌΠ°ΠΊΡΠΈΠΌΠ°Π»ΡΠ½ΠΎΠΉ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ (Tmax) Π² ΠΏΠ»Π°Π·ΠΌΠ΅ ΠΊΡΠΎΠ²ΠΈ ΠΈ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΠΎ Π±ΠΎΠ»ΡΡΠ΅Π³ΠΎ Π·Π½Π°ΡΠ΅Π½ΠΈΡ ΠΌΠ°ΠΊΡΠΈΠΌΠ°Π»ΡΠ½ΠΎΠΉ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Π΄Π΅ΠΉΡΡΠ²ΡΡΡΠ΅Π³ΠΎ Π²Π΅ΡΠ΅ΡΡΠ²Π° Π² ΠΊΡΠΎΠ²ΠΈ. Π ΡΠΎ ΠΆΠ΅ Π²ΡΠ΅ΠΌΡ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠ°Ρ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΡ Π³Π°ΡΠΌΠΈΠ½Π° Π½Π΅ ΠΎΠΊΠ°Π·ΡΠ²Π°Π΅Ρ Π·Π½Π°ΡΠΈΠΌΠΎΠ³ΠΎ Π²Π»ΠΈΡΠ½ΠΈΡ Π½Π° ΡΠ°ΠΊΠΎΠΉ ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡ, ΠΊΠ°ΠΊ ΠΏΠ»ΠΎΡΠ°Π΄Ρ ΠΏΠΎΠ΄ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠΊΠΈΠ½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΡΠΈΠ²ΠΎΠΉ, ΡΡΠΎ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΠ΅Ρ ΠΎΠ± ΠΎΡΡΡΡΡΡΠ²ΠΈΠΈ ΡΠ°Π·Π½ΠΈΡΡ Π² ΡΡΠ΅ΠΏΠ΅Π½ΠΈ Π°Π±ΡΠΎΡΠ±ΡΠΈΠΈ Ρ ΡΡΠ°Π²Π½ΠΈΠ²Π°Π΅ΠΌΡΡ
Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΡΠΎΡΠΌ