[STUDY OF THE CYTOTOXIC ACTIVITY OF INDOLE ALKALOIDS FROM THE ABOVEGROUND ORGANS OF VINCA ROSEA L. INTRODUCED IN WESTERN GEORGIA].

The objects of this research were the aboveground and underground parts of Vinca rosea L., a species of periwinkle introduced in Western Georgia. The sum of alkaloids and biologically aactive fractions of monomeric alkaloids were obtained by liquid-liquid extraction, precipitation with petroleum ether (I), polybuffer distribution (II) and 10% acetic acid (III). 14 known compounds were identified by LC-MS/MS and GC/MS: Low molecular weight compounds (М+226, М+202, №1,2, М+168) and alkaloids Ajmalicine, Tetragidroalstonine, C20-dihydrova llesiahotamine, C19-C20 Vallesiahotaminole, Vallesiahotamine lacton, Polyneuridine, Pericy clivine, Lochnerame, Norharmane, Vidorosine, Vindolinine, Isovindolinine, Akuammicine. The cytotoxicity of monomeric alkaloids was evaluated for A-549 (cells of the lung cancer line), DLD-1 (cells of the rectal adenocarcinoma line) and W-1 (cells of the normal human fibroblast line). All three substances (I, II, III) showed pronounced cytotoxic activity.

[BIOLOGICALLY ACTIVE ALKALOIDS FROM RHIZOMES WITH ROOTS OF VINCA HERBACEA WALDST. ET KIT, GROWING IN GEORGIA].

Roots and rhizomes of Vinca herbacea Waldst. et Kit, were collected during early flowering and fruiting. Рhenophases biologically active substances I and II were obtained by liquid-liquid extraction. Dominant alkaloids: tabersonin, reserpine, maidine, norfluorocurarin and copsinin were obtained after the dispertion in citrare-phosfhate buffer and subsequent TLC. Accelerated restitution of granulocytopoiesis was observed in mice during both irradiation and myelotoxic drug-induced acute leucopenia. Increase in total WBC over 200% was observed after treatment by substance I in drug-induced leucopenia model (fivefold oral administration) and over 130% after treatment by substance I in irradiate mice (fivefold intraperitoneal administration). Morphological and anatomical structures of the underground organs of V. herbacea have been studied. The main microstructural characteristics are revealed - Rhizomes are characterized by coutinized epidermis, lamellar collenchyma, fibers and the texture of the vascular system of a monocyclic structure. The root system shows the whole cortex, the endoderm with Kaspar spots; the outer, radially continuous phloem tissue is located in the conducting system and distinguishes the cylindrical xylem tissue with annular and spiral-circular blood vessels.

[SCREENING OF WILD SPREAD AND CULTIVATED OF BUXUS SPECIES GROWING IN GEORGIA ON THE CONTENT OF ALKALOIDS AND BIOLOGICAL ACTIVITY].

Georgian flora is represented by about 4150 plant species. Many important alkaloid-containing plant species and among of them are species Buxus L. of genus in Adjara. The aims of the research were: sequential screening of the plants for the consistence of alkaloids; Study of anatomical characteristics of Buxus colchica Pojark. and revealing of specific pharmacological activity of steroidal alkaloids. The objects of research were B. colchica, B. balearika and B. sempervirens, growing in Adjara (Georgia), collected in active phase of flowering of the plants. There were revealed 370 species of alkaloid containing plants. Sum of alkaloids and crude aqueous extract have spasmolitic and antihistaminic activity. Experimental anatomical research of diagnostic characteristics of the bines showed the existence of monocyclic transient system with fiber like tracheids, dorsoventral mesophyll of the leaves; the structure for the upper part of epidermis is linear and the lower part is curved, type of stomata is paracitic.

[ALKALOIDS OF PEGANUM HARMALA L. AND THEIR BIOLOGICAL ACTIVITY].

Peganum Harmala L., Peganасеае widely distributed in Georgia. On the basis of chemical analysis of the composition of alkaloids it was found out that the plant contains quinazoline derivatives, among which dominats alkaloid d, 1 peganine: С11Н12NО2, m.p. 198-99ºC (СН3ОН). UV, λmax 275 (lgε 3,95). In IR-spectrum (KBr) 1625 cm- (-N=C) 3200-370 (OH)cm-1 . Mass- spectrum: М+ 171(100%). It was studied the dynamics of accumulation for total alkaloids and d, l - peganine: in the budding phase the amount of alkaloids was - 3,71%, d, l - peganine 0,07÷0,09%; in the phase of mass flowering the sum of alkaloids - 4,51% ,d, l - peganine - 0,1÷0,13%; in the phase of ripeness total alkaloids - 3.92%; d,l - peganine - 0,08÷0,1. The study of specific pharmacological activity showed that the d,l - peganine similar to peganine at a dose of 30 mg/kg causes a decrease in heart rate by 30÷40 beats/min, which is characteristic for anticholinesterases, in parallel with this, a decrease in cholinesterase activity in blood serum has been observed.

[Analysis of some species of magnolia introduced to west georgia, on content of aporphine alkaloids and their biological activity].

The goal of research was study of vegetative organs of Magnolia species introduced to west Georgia on qualitative and quantitative content of aporphine alkaloids and evaluate cytotoxic activity of total alkaloids from M. officinalis and M. glauca against A-549, DLD-1 and WS-1. Qualitative and quantitative content of aporphine alkaloids in different vegetative organs were determined by chromatographic methods. Based on the researches alkaloids - liriodenine and lanuginozine are characteristic for leaves, for bark of branches - liriodenine, d-caaverine; for bark of trunk - a liriodenine, a caaverine and a magnoflorine. Liriodenine may be considered as is chemotaxonomic sign of genus Magnolia, as it was found in all analyzed vegetative organs. In vitro cytotoxic activity of total alkaloids of M. officinalis and M. glauca has been investigated against DLD-1, WS-1 and A-549. Total alkaloids of M. glauca expressed significant cytotoxic activity against DLD-1 and WS-1, and medium cytotoxicity against A-549; M. officinalis exerted middle activity against A-549, DLD-1, WS-1.

[Alkaloids of Vinca rosea L. introduced to Western Georgia].

Vinca roseae L. (Саtharanthus rosea (L.) G. Don) was introduced at Kobuleti experimental station of medical plants. The object of investigation was the plant material of Vinca roseae L. collected in May, 2005., September, 2006 and October, 2009. Total alkaloids were obtained in accordance with Atta- ur-Rachman method. The variability of the quantitative and qualitative composition of total alkaloids and vincaleikoblastin (VLB) fraction during vegetation was studied. It was established that the maximal content of total alkaloids and VLB fraction of Vinca roseae L. is accumulated in the phase of secondary flowering, hence the collecting of a plant material is recommended to be made during the aforesaid vegetation phase as for this period it is a rather high output of a raw material, alkaloid complex and VLB faction. Alkaloids vinkaleikoblastin, ajmalicine and new epimer tetrahydroalstonine with С3Н-α- orientation were yielded, separated and identified using modern physical-chemical and spectral methods (13С NMR).

[Study on the separation process of pharmacological active total alkaloids from Chelidonium majus L. growing in Georgia].

In present article was studied the separation process of pharmacological active total alkaloids from Chelidonium majus L. growing in Georgia. Alkaloids were extracted from medicinal herbal material and separated by liquid extraction, diluents gas and a microfiltration through membrane equipment. The obtained A1, A2, A3 fractions were analyzed by GC/MS method; in all cases separation proceeds by the principle of extraction of the target alkaloids. It was concluded that the A1 is enriched with α and ß cryptopins, and protopin, but homochelidonine and chelidonine are in low contents. As accompanying alkaloid is identified dihydrosanguinarine as an artifact; the A2 is enriched with the maximum contents of stylopine and protopin, but the poor contents of chelidonine and homochelidonine; the A3 is enriched with α and ß cryptopins and maximum content of chelidonine. Extraction of alkaloids from Chelidonium majus L. proceeds selectively, but depending on a way of separation of the total alkaloids allows varying qualitative and quantitative consistence of the final product.

Development of solid, dosage forms of medicinal drugs from indoline group alkaloids.

According to biopharmaceutical investigations, the regimen of the tablets of alkaloid containing new galenic preparation of indoline and indole group - Vinkabral, Vingerbin has been developed. Also, the preparation technology was worked out and it has been defined that optimal method of tabletting new galenic formulations, such as Vincabral and Vingerbin is direct pressing by using polifunctional additional formulations - Proslov SMCC (siliced methylceluslose) and Glikonat Sodium of Starch. Their influence on the technological characteristics are studied, so as the proportion of additional compounds are defined. The influence of technological parameters on technological characteristics of the tablets Vinkabral, Vingerbin were investigated and optimal conditions were selected: optimal humidity was 1.5-3.0%, Optimal compression power-105-120 mpa. The kinetics of the release of active substance - alkaloids from the tablets of Vinkabral and Vingerbin was studied using the methods of "rotary basket" in sour, neutral and alkaline area during the mix time 50 rt/min and 100 rt/min. The 90% of active substance releases in sour area during 75 minutes in 100 rt/min mix up condition.

Tableting technology from the individual and new galenic alkaloid consisting preparations of the Phellodendron lavallei bark.

The aim of the research was to work out the technology and tablet composition from new galenic preparations consisting of alkaloids of the bark of Phellodendron lavallei and hydrochloride of berberin on the base of complex research. The bark of the Phellodendron lavallei introduced in Georgia contains alkaloids, from which 2% is berberine used for curing chronicle hepatitis, hepatic cholecystitis and bilestone disease. The structural-mechanical and technological character of tablets and their masses were defined by the known methodic. Friability was studied by defining the fluctuation and bending corner. Volume density was established by using vibration cylinder. Volume density of powders was studied by pyknometers. Porosity was calculated by the bearing of volume density of the masses. The size of pressing was established by defining the firmness of tablets. The granule composition was defined by analysis. On the basis of studying technological and physical-chemical character features of the substances of new galenic preparations and individual substances consisting of alkaloids got from the bark of Phellodendron lavallei, it is scientifically proved and practically offered optimal technological parameters of tablets forming process and recipes.

[Extraction of pharmacologically active alkaloids from Vinca species].

From the Genius Vinca the drugs have been received, arbitrally named: Vingerbin- with anthyarithmic activity, Vincabral-for improvement of brain blood circulation and leicobetin-as stimulator of leicopoesis. The investigations has been performed for creation of rational, resource saving, rentable phyto technologies. As a result, the liquid extraction general schema is provided for receipt of indolic alkaloids from plants V. herbaceae and V.minor. Analyses have shown that extraction with diluent gaz gives the possibility to receive the sums rich with alkaloids:Vingerbin and Vincabral. The advantage of extraction with diluent gaz is exclusion of high volumes of organic and non organic chemicals on the stage of extraction from raw material and liquid extraction, and remain and lipofil fraction converse to new phytosubtances for receipt of biologically active flavonoids, amino acids etc.