Project №АР05134198 «The study of the biosynthesis January – December 2019 of terpenoids in and the search for new pharmacologically active bimolecular compounds» In 2019, the Research Institute of Biological Safety Problems took part in the implementation of this project.

For chemical modification, sesquiterpenic lactones of Based on the isolated terpenoids, flavonoids and alkaloids, For the reporting period, an application was filed for a grossheimin from Chartolepis intermedia Boiss., arglabin new hybrid derivatives were synthesized for the first time: receiving of protection document 2019/0611.1 dated and argolide from the CO2 extract of Artemisia glabella Kar. quercetinylgrossheimin (according to the Heck reaction) and 22.08.2019. Hydrochloride 3-oxo-8α-hydroxy-1,5,7α, et Kir., flavonoids pinostrobin from an alcoholic extract of β-cytisinylgrossheimin (according to the Michael reaction). 4,6,8,11β(H)-guaia-10(14)en-11(13-cytisinyl)-12,6-olide, Populus balsamifera L. buds and quercetin from an alcoholic Based on sesquiterpene lactones arglabin and grossheimin, which has an anthelmintic activity. extract of Hypericum perforatum L. were isolated and 4 of their new cytisinyl and anabasinyl derivatives were accumulated. synthesized. Grossmizin oxime was developed as the initial synton for chemical modifications.

Amounts of extractive substances were accumulated from 5 In experiments conducted at the Research Institute of 2 articles were published in peer-reviewed foreign journals species of plants (Artemisia santolinifolia Turcz. ex Besser, Biological Safety Problems (under agreement No. 48 of with impact factor: Ferula ovina Boiss., Ferula kelleri Koso-Pol., Ferula March 27, 2019), leaves and buds of Artemisia glabella Kar. Molecules. – 2019. – Vol. 24, No 350. – P. 1-18 .(Impact songarica Pall. ex Spreng, trichophylla (Schrenk.) et Kir. were determinated as terpenoid-containing organs. Factor according to Web of Science database 3.38); Heimerl). From the sum of extractives of Ferula kelleri Koso- Promising genes of syntheses GAS, GAO, and COS of the Expert Opinion on Therapeutic Patents. – 2019. - Vol. 29, Pol. the new natural compound 5-(1-ethoxyvinyl)-2-methyl- biosynthetic pathway of sesquiterpenic lactones were No 9. – P. 689-702 (Impact Factor according to Scopus benzene-1,3-diol was isolated and the structure of the its identified in them for the first time. A comparative analysis of database 1.318); molecule was established, and the ester of aromatic acid the obtained sequences in BLAST showed their high (more Abstracts of 3 reports in the collection of the XIII and terpenoid alcohol of the humulan structure, ferocinin, than 90%) identity with the genes of the enzymes of the International Symposium on the Chemistry of Natural was identified. From Artemisia santolinifolia Turcz. ex Besser GAS/GAO/COS module of other Compounds October 16-19, 2019, Shanghai, China and the coumarin scopoletin was isolated and identified, from representatives. Data on genes-"candidates" for GAS and International Scientific and Practical Conference “Actual Handelia trichophylla (Schrenk.) Heimerl - dimeric COS isolated from Artemisia glabella Kar. et Kir., will be Problems of Biodiversity and Biotechnology”, October 1, sesquiterpene lactone handelin. published in the Information Base of NCBI National Center 2019. for Biotechnological Information (USA).

The structure of the isolated compounds and synthesized According to the results of bioscreening, α- * JSC International Research and Production Holding new derivatives was established on the basis of the data of cytisinylgrossheimin hydrochloride is a promising compound “Phytochemistry”, under the Agreement with the Committee of Science of the MES RK No. 79 dated March 2, 2018, implements grant projects IR-, UV-, 1H, 13C NMR spectroscopy and X-ray diffraction for an in-depth study of its anthelmintic activity. for 2018-2020 in priority areas "Science of Life and Health" and analysis. "Rational use of natural, including water resources, geology, processing, new materials and technologies, safe products and structures“ Project №АР05133096 «Pharmacognostic research of January – December 2019 plants and taxon chemosystematics of the Asteraceae family» Co-executing organizations took part in the implementation of this project: Institute of Botany and Phytointroduction and the Central Siberian Botanical Garden of the SB RAS.

A comparative analysis of the anatomical and morphological Together with the Central Siberian Botanical Garden of the Locations of growth have been identified and operational and diagnostic features, as well as the results of SB RAS (under Agreement No. 57 of April 10, 2019) and the reserves of Artemisia annua L. have been assessed in the histochemical studies of 6 species of plants of the subgenus Institute of Botany and Phytointroduction (under Agreement villages of , Shilikbai of Zhambyl district, in the Artemisia Less (Artemisia absinthium L., Artemisia annua L., No. 55 of April 01, 2019), a comparative analysis of vicinity of the villages of Sayan, Kainar and of the Artemisia frigida Willd., Artemisia rupestris L., Artemisia anatomical and morphological and diagnostic features as Karasai district, in the villages of Akshi, Avat, Turgen and sieversiana Ehrh. Ex Willd., Artemisia santolinifolia Turcz. ex well as the results of histochemical studies of 5 species of Enbek of Enbekshikazakhskyi district of . Besser.) was carried out. Differences were revealed in the plants of the subgenus Dracunculus (Bess.) Rydb. The integrity of raw materials was determined, shape of the stem, leaves, the number and structure of (Artemisia dracunculus L., Artemisia quinqueloba Trautv., merchandising parameters of plants of the Artemisia L conducting bundles, pubescence (presence or absence, type Artemisia marschalliana Spreng., Artemisia scoparia Waldst. were established. of hairs), and the shape of epidermal cells, which are the & Kit., Artemisia tomentella Trautv.) was carried out. It was hallmarks of plant species. For the first time, the results of a revealed that the studied species differ in stem shape, leaf histochemical study on cross-sections of leaves and surface shape, number and structure of conducting bundles, preparations of flowers of the studied plants were obtained; pubescence (presence or absence, hair type), stomatal the presence of terpenoids and polyphenolic compounds apparatus type, form of epidermal cells. According to the was revealed. results of histochemical studies of cross-sections of leaves and surface preparations of flowers of the studied plants, the content of terpenoids, coumarins and polyphenolic compounds was determined. A pharmacognostic study and standardization of Peganum According to the results of the study of sesquiterpene For the reporting period, an application was filed for a patent harmala L. raw materials was carried out, an analytical lactones and coumarins of the species of subgenus of the Republic of . Application No. 2019/0484.1 regulatory document “Peganum harmala, roots” was Artemisia Less. and Dracunculus (Bess.) Rydb., dated July 9, 2019 “Method for the obtaining of regenerated developed. representatives of these classes of natural compounds are plants Centaurea bipinnatifida (Trautv.) Tzvel.” defined as chemotaxonomic markers of studied taxa. 2 articles were published in journals Plant resources. – 2019. – Vol. 55, №3. – P.334-342 (impact factor RSCI - 0.331). News of the National Academy of Sciences of the Republic of Kazakhstan. Series of biology and medicine – 2019. - №2 - Р. 42-48 (according to Kazakhstan citation base 0,036). Project №АР05130476 «Technology of water-soluble January – December 2019 substances and finished dosage forms based on natural flavonoids and terpenoids»

The effect of mechanochemical processing on the water A one-stage technology has been developed for producing a The technology for producing a complex of pinostrobin solubility of arglabin native substance was studied. An water-soluble substance of arglabin by mechanochemical oxime with disodium salt of glycyrrhizic acid and increase in the proportion of polysaccharide in a mixture of processing of arglabin native with an auxiliary substance - mechanocomposite of arglabin native with arglabin with arabinogalactan slightly increases the solubility polyvinylpyrrolidone, in a ball mill with a steel drum for 1 polyvinylpyrrolidone was optimized. of the mechanocomposite. It was found that during hour, in which the mechanocomposite of arglabin native mechanoprocessing, there is no disordering of the crystal dissolves within 20 minutes. structure of arglabin and its molecular dispersion in the polysaccharide matrix.

Laboratory regulations have been developed and approved Experimental-industrial regulations for the production of For the reporting period, a conclusion was received from for the production of a complex of pinostrobin oxime with complex of pinostrobin oxime with disodium salt of 17.10.2019 on the grant of a patent of the Republic of disodium salt of glycyrrhizic acid LR-40761819-02-19 and a glycyrrhizic acid OPR FD65005037R-05-19 and Kazakhstan on the application 2018/053.1 dated 26.07.2018 mechanocomposite of arglabin native with mechanocomposite of arglabin native with "Method for producing a water-soluble substance based on polyvinylpyrrolidone LR-40761819-03-19. polyvinylpyrrolidone OPR FD65005037R-06-19 were pinostrobin oxime." developed and introduced into pharmaceutical production of An application is filed for a patent No. 2019/0775.1 dated LLP "Karaganda Pharmaceutical Plant". 22.10.2019 "Water-soluble mechanocomposite based on arglabin native". Abstracts are published in the collection of the XIII International Symposium on the Chemistry of Natural Compounds October 16-19, 2019, Shanghai, China. Project №АР05130956 «Pharmacogenetic study of January – December 2019 terpenoid molecules and molecular genetic mechanisms of their action» The Institute of Genetics and Cytology took part in the implementation of this project.

Based on the isolation of HRAS proteins from tissue In the treatment group with drug "Arglabin", 80.6% of non- Negative expression of H-Ras during immunohistochemical samples of patients with breast cancer, protein specific infiltrative carcinomas were found, in the group with studies was statistically significantly predominant in patients concentrations values ranging from 0.26 mg/ml to 1.38 the standard AS regimen (adriablastin + cyclophosphamide) with luminal type A (p = 0.04) and thrice negative type (p = mg/ml were obtained. By denaturing electrophoresis, a - 73.7%, and among patients with monotherapy with drug 0.01). fraction containing 90% of the target HRAS protein was "Arglabin" - 70.9%. In the group of patients with Her2/neu positive non-luminal determined. The final yield of the target protein was 1.38 mg. type, positive expression of H-Ras oncoproteins prevailed (p = 0.002).

A study of immediate efficacy indicators showed that Given that the drug "Arglabin" blocks the enzyme The Institute of Genetics and Cytology (under Agreement neoadjuvant drug therapy was significantly more effective in farnesylprotein transferase, as a result of which H-Ras No. 88 of July 17, 2019) established a quantitative patients with breast cancer without expression of H-Ras proteins cannot transmit signals to the tumor cell for determination of Western blot analyzes of the H-Ras oncoproteins (p˂0.05). proliferation and progression, it was found that with positive oncoprotein in patients with breast cancer using the ImageJ expression of H-Ras oncoproteins and the effect of complex program. The beta-Actin protein was used as a control. It therapy in combination with Arglabin and in an independent was found that the percentage ratio of the expression of the regime, the rates of relapse-free survival rates are H-Ras oncoprotein in patients with breast cancer according statistically higher than when treated with only the standard to the ImageJ program varies from 1.3 to 66.6%. AC regimen (adriablastin+ cyclophosphamide).

For the reporting period scientific article in the journal "Medicine and Ecology". - 2019. - No. 1. - P.8-14 (Impact factor according to the Kazakhstan citation base 0.042), abstracts of 2 reports in the materials of the 4th Russian Conference on Medical Chemistry with international participation of MedChem Russia 2019, June 9-14, 2019, Yekaterinburg and IV International Scientific practical conference "Global science and innovations 2019: Central Asia", January 21, 2019, Astana, were published. Project №АР05134907 «Molecular docking and January – December 2019 bioscreening of new natural compounds»

To select compounds-candidates of potential drugs with Based on the results of docking, compounds were selected Based on molecular docking data, biological studies of neurotropic effects, computer simulation of the binding that demonstrated relatively high and potentially promising samples of natural alkaloids and their derivatives were energy of the “ligand-target” complex (docking) was values of the interaction energy of the molecule with the carried out in vitro and in vivo model systems. performed for 23 molecules of the beta-carboline alkaloid dopamine D2 receptor and the MAO-A and MAO-B harmine isolated from Peganum harmala L. and its enzymes. Thus, as a result of molecular docking, it was semisynthetic derivatives with the DRD2 receptor, which is found that the alkaloid compounds 9-methoxy-2-phenyl-11H- one of the five known types of dopamine receptors, indolisino[8,7-β]indole, 8-acetylharmine, 2-(3,4- According to the results of experimental studies of the belonging to the class of D2-like receptors and inhibiting dichlorophenyl)-9-methoxy-11H-indolisino[8,7-β]indole, ((E)- neurotropic activity of alkaloid compounds in experimental adenylate cyclase, as well as the MAO-A and MAO-B 1-(7-methoxy-1-methyl-9H-pyrido[3,4-b]indol-8-yl)-3-(2, 4 stress models in vivo, it was revealed that the alkaloids 8- receptors (monoamine oxidase A and B), which are about dimethoxyphenyl)prop-2-en-1-one have a comparatively acetylharmine, ((E)-1-(7-methoxy-1-methyl-9H-pyrido[3,4- two of the key enzymes that provide metabolization of strong bond with the D2 dopamine receptor. Compounds 9- b]indol-8-yl)-3-(2,4-dimethoxyphenyl)prop-2-en-1-one, biological precursor dopamine. methoxy-2-phenyl-11H-indolisino [8,7-β]indole, 2-F-chalcon lappaconitine, cytisine at a dose of 5 mg/kg show a derivative of harmine have a relatively strong bond with the neurotropic effect, increasing the level of the orientational enzyme monoamine oxidase B (MAO-B). Alkaloids 2-(3,4- reaction, normalizing the emotional state, lowering the level dichlorophenyl)-9-methoxy-11H-indolisino[8,7-β]indole, 9- anxiety and fear in animals. methoxy-2-(4-methoxyphenyl)-11H-indolisino [8,7-β] indole, chalcon derivative of harmine, 3-acetyl-9-methoxy-2-phenyl- 11H-indolisino [8,7-β]indole, 9-methoxy-2-phenyl-11H- indolisino [8,7-β]indole have the strongest bond with the enzyme monoamine oxidase A (MAO-A). The prospect of further in-depth study of the above-mentioned alkaloid compounds as neurotropic agents was revealed.

For the reporting period, an article was published in the The cytotoxicity of samples of alkaloids and their derivatives The analgesic activity of natural alkaloids and their journal «News of the National Academy of Sciences of the was studied in vitro in the survival test of larvae of marine derivatives was evaluated in vivo in the "acetic-induced Republic of Kazakhstan». - Series of biological and medical.- crustaceans Artemia salina (Leach). It was experimentally writhing" test. The analgesic activity of samples of 2-F- 2019.-№3.- Р.56-63 (Impact-factor according to Kazakhstan established that samples of alkaloids 2-F-chalcone derivative chalcone derivatives of harmine and cytisine at a dose of 10 citation base 0.036). of harmine, hydrazone derivative of harmine, N-(2)-(3,4- mg/kg was established, comparable with the comparison dichlorophenacyl) harminium bromide show cytotoxicity drug "Diclofenac sodium”. against larvae of marine crustaceans Artemia salina (Leach). Project №AP05130575 «Development of effective January – December 2019 methods for the isolation and identification of new biologically active compounds from plant’s essential The co-executors of this project are the Novosibirsk Institute of Organic Chemistry of SB RAS and the Novosibirsk National Research State oils» University.

The qualitative composition and quantitative content of Using microwave extraction method, essential oils were Essential oils were isolated from Ferula Kelleri Koso-Pol., components in the samples of essential oils of 9 plant isolated, for the first time, from Artemisia santolinifolia Schrenkia vaginata (Ledeb.) Fisch. & C.A. Mey, Viola canina species was studied. Moreover, using modern gas Turcz. ex Bess., Ajania fastigiata (C.Winkl.) Poljak., L. and studied their qualitative composition, quantitative chromatography methods with a flame ionization detector in Artemisia rutifolia Steph.ex.Spreng., Ferula ovina (Boiss.), content by gas chromatography with a flame ionization combination with mass spectrometry, 333 components were Ferula Kelleri Koso-Pol., Ferula songariсa Pall. ex Spreng. detector and mass spectrometry. From the essential oil of found in the studied essential oils, of which 187 compounds Ferula foetida Linn., 2,3,4,5-tetramethylthiophene and were identified. guaiole were isolated and identified. Using the rectification method of essential oils of Thymus Marschallianus Willd. and Origanum vulgare L., followed by chromatographic purification of fractions, monoterpene phenols thymol and carvacrol were isolated. For the first time, new esters of L-menton oxime were Essential oils, isolated from Ferula Kelleri Koso-Pol., Ferula During the reporting period, 3 articles were published in synthesized: acetyl oxime of L-menton, propionyl oxime of L- songarica Pall. ex Spreng., Ajania fastigiata (C.Winkl.) foreign journals with impact factor: menton and butyryl oxime of L-menton. Poljak., Ferula ovina (Boiss.) and Artemisia santolinifolia Chemistry of natural compounds.-2019.-№5.-Р.833-834 Turcz. ex Bess. exhibit moderate antimicrobial activity. (Impact- factor based according to Scopus database 0,508) Essential oils from Ferula Kelleri Koso-Pol., Ferula songariсa Natural Product Research. - 2019. – Sep. 23.-P.1-4. Pall. ex Spreng., Artemisia santolinifolia Turcz. ex Bess., (Impact- factor based according to Scopus database 1.999). Ajania fastigiata (C.Winkl.) Poljak. have moderate anti- Journal of Applied Botany and Food Quality. – 2019. – inflammatory activity. Vol.92. – Р. 39 – 48. (Impact- factor based according to Scopus database 1.106). An article in the domestic journal included in the Scopus database: Eurasian Chemico-Technological Journal. - 2019. – Vol.21, № 4.- С.300-308 (Impact- factor based according to Scopus database 0.13). Abstracts of 2 reports in the collection of the XIII International Symposium on the Chemistry of Natural Compounds October 16-19, 2019, Shanghai, China. Project №АР05133718 «Synthesis, structure and biological January – December 2019 activity of new water-soluble derivatives of polyoxysteroids»

By the quantum-chemical method of the density functional 2-deoxyecdysterone was, for the first time, isolated from the Mathematical modeling of biological activity using the PASS DFT/B3LYP/6-31G the geometric, energy and electronic aerial part of the Silene fruticulosa (Pall.) Schischk (family program was carried out and a strategy for the targeted parameters of 2-deoxyecdysterone were calculated. A Caryophyllaceae Juss.). Using NMR spectroscopy, we production of hybrid mixed ligand complexes based on comparative analysis of the physicochemical properties of studied its complex formation with γ-cyclodextrin. By steroid and flavonoid molecules was developed. the molecules of 2-deoxyecdysone, 2-deoxyecdysterone and changing the chemical shifts of the protons of the substrate ecdysterone-synthons for regioselective modifications was and the receptor, it was found that a supramolecular conducted. Virtual bioscreening of indicated complex of inclusion of stoichiometric composition 1: 1 with phytoecdysteroids was carried out. the entry of fragment A of the substrate molecule into the internal cavity of the receptor is formed. Based on 2,3,22-acetoxy-14,20,25-hydroxy-5,9 (H)-cholest- 0.8 g of ecdysterone from the extract of the aerial part of As a result of bioscreening, it was found that a new 7-en-6-one, a new derivative was synthesized for the first Silene wolgensis (Hornem) Bess. Ex Spreng with its high supramolecular complex of 2,3,22-acetoxy-14,20,25- time, for the molecule of which a thin and spatial structure content (4.0%) was synthesized preparatively for the hydroxy-5,9 (H)-cholest-7-en-6-one with a β-cyclodextrin in a was established. synthesis of new heterocyclic compounds on its basis. dose of 25 mg/kg has anti-inflammatory activity on the model of acute exudative reaction. For the first time, the water solubility of 2-deoxyecdysone and its α-, β-, and γ-complexes was studied in different ratios.

The behavior of copper (II) in the presence of a modified The heterocyclic compound 2-chloro-2-oxo-1,3,2- For the reporting period, 2 articles were published in foreign phytoecdysteroid and a number of flavonoids: ecdisterone dioxophospholane ecdysterone and 2 heterocyclic amide journals with impact factor: oxides, pinostrobin, quercetin, myricetin was studied for the derivatives based on it were synthesized for the first time Steroids.- 2019. – Vol. 147.-P. 37-41 (Impact Factor first time, 3 new hydrophilic mixed ligand complexes and their structures were established. according to Web of Science database 2.523) combining phosphorus and nitrogen containing fragments in 2. Russian Journal General Chemistry. -2019. Vol.89. – their structure were synthesized. Iss.3. P.424-428. (Impact Factor according to Scopus The antiradical activity of mixed ligand complexes of database 0,658). ecdysterone oximes and a number of flavonoids with copper An article in a peer-reviewed domestic scientific publication (II) was studied for the first time. with a non-zero impact factor: Bulletin of the Karaganda University.-2019. - №1(93). -Р. 39-47 (Impact factor according to Kazakhstan citation base 0.068). Abstracts of 3 reports in the collection of the XIII International Symposium on the Chemistry of Natural Compounds October 16-19, 2019, Shanghai, China. Project №AP05130781 «Isolation from plants, identification and January – December 2019 structural modification of flavonoids - the basis of new drugs»

Chemical screening of 10 species of plants of the flora of The most promising plant sources of polyphenolic A chemical study of Tanacetum vulgare, Crataegus Kazakhstan for the content of flavonoid compounds was compounds have been identified, such as Silybum marianum sanguinea, Bidens tripartita, Larix sibirica was carried out. At carried out, including Origanum vulgare, Silybum marianum, (flavonoid content from 1,5 to 4%), Crataegus sanguinea the same time, flavonoid samples were isolated and Carduus nutans, Hypericum perforatum, Achillea millefolium, (flavonoid content from 0,89 to 1,39%), Hypericum developed: apigenin, quercetin, kaempferol and Tanacetum ulutavicum, Rosa spinosissima, Phaseolus perforatum (flavonoid content from 2 to 4%). dihydroquercetin. vulgaris, Hippophae rhamnoides and Crataegus sanguinea. In this case, the qualitative composition and quantitative content of polyphenolic compounds in extracts of these plants was determined. In terms of producing biologically active compounds based Biological screening of extracts, samples of flavonoids and Laboratory regulations for the production of pinostrobin on flavonoids, 4 new derivatives were synthesized, the their derivatives for antioxidant and antiradical activity was acetate substance have been developed. molecular structure of which was established on the basis of carried out. It was found that the studied compounds and physicochemical constants, data of IR-, UV-, 1H and 13C extracts have biological activity. NMR spectra.

For the reporting period, an article was published in the collection of scientific papers: “Current Trends in the Development of Health Care Technologies.” - VILAR, Moscow, 2019. Project №АР05135304 «Chemical study of alkaloid plants as January – December 2019 promising sources of biologically active substances».

According to the results of a chemical study of plants of the A chemical study of plants of the genus Aconitum L. made it 5 new derivatives of harmine, the molecular structure of families Ranunculaceae Juss.: Aconitum soongaricum possible to isolate and identify diterpene alkaloids - aconitin, which is established on the basis of elemental analysis and Stapf., Aconitum monticola Steinb., Aconitum anthoroideum songorine, delcosine from Aconitum soongaricum Stapf., spectral data (UV-, IR-, 1Н-, 13С-, 19F-NMR) were DC., Aconitum altaicum Steinb., sums of extractives songoramine, delcosine, atisinium chloride from the roots of synthesized. containing alkaloids are isolated. Aconitum monticola Steinb., aconitine from the aerial part of Aumitum alconitum Steinb. For the first time from Aconitum anthoroideum DC., growing on the territory of Kazakhstan, the previously well- known alkaloid, delcosine, was isolated and identified. As a result of bioscreening of samples of isolated and The results of studies of neurotropic activity showed that For the reporting period, an article was published in a foreign synthesized compounds, it was found that 2-fluorochalcone-, 2,3,4-trimethoxychalcone-, 2-fluorohydrazone derivatives of journal with impact factor: Chemistry of Heterocyclic 8-acetylhydrazone-, N-(2)-(3,4- harmine at a dose of 10 mg/kg show neurotropic activity in Compounds. – 2019. -Vol.55. -Iss.2. - Р.135-141. (Impact dichlorophenacyl)harminiumbromide derivatives of harmine the Porsolt's "despair test". 8-acetylhydrazone derivative of factor according to Scopus database 1,201) and abstracts of show moderate antibacterial activity against gram-positive harmine, N-(2)-(3,4-dichlorophenacyl) harminiumbromide 2 reports in the collection of the XIII International Symposium test strains of Staphylococcus aureus, Bacillus subtilis. The and 9-methoxy-2-(4-methoxyphenyl)-11H-indolisino[8,7- on the Chemistry of Natural Compounds October 16-19, 2-fluorochalcone-, 2-fluoropyrazoline-, 2,3,4- β]indole at a dose of 10 mg/kg did not show neurotropic 2019, Shanghai, China. trimethoxychalcone derivatives of harmine show a activity in the Porsolt's "despair test". moderately pronounced antibacterial activity against the gram-negative strain of Escherichia coli. The 4- methoxychalcone derivative of harmine, as well as the diterpene alkaloids delcosinу and lappaconitine, have antimicrobial activity against the presented gram-positive test strains.