The Eurasian National University named after L.N. Gumilyov will defend the thesis for the degree of Doctor of Philosophy (PhD) by Turgunbayeva Aiman on the topic «“Chemical composition and biological activity of some extracts and metabolites of Rheum tataricum L.fil”» under the educational program «8D05306 – Chemistry».
The dissertation was carried out at the «Chemistry education department» of L.N. Gumilyov Eurasian National University.
The language of defense is kazakh
Official reviewers:
Eskalieva Balakyz Kymyzgalievna – Candidate of Chemical Sciences, Professor, Non-Profit Joint-Stock Company “Al-Farabi Kazakh National University” (Almaty, Republic of Kazakhstan);
Ibraeva Manshuk Muratovna– PhD, Associate Professor, Non-Profit Joint-Stock Company «Yessenov University» (Aktau, Republic of Kazakhstan).
Temporary members of the Dissertation Council:
Numonov Sodik Rakhmonovich – Doctor of Natural Sciences, Scientific Research Institute “Chinese-Tajik Innovation Center for Natural Products” (Dushanbe, Republic of Tajikistan);
Atazhanova Gayane Abdulkhakimovna – Doctor of Chemical Sciences, Professor, Сorresponding member of the National Academy of Sciences of the Republic of Kazakhstan, Non-Profit Joint-Stock Company “Karaganda Medical University” (Karaganda, Republic of Kazakhstan);
Ibataev Zharkyn Abykenovich – Candidate of Chemical Sciences, Docent, Non-Profit Joint-Stock Company “S. Seifullin Kazakh Agrotechnical Research University” (Astana, Republic of Kazakhstan).
Scientific advisors:
Sultanova Nurgul Adaybayevna – Doctor of Chemical Sciences, Professor, Department of Chemistry, , Non-Profit Joint-Stock Company “L.N. Gumilyov Eurasian National University” (Astana, Republic of Kazakhstan);
Shults Elvira Eduardovna – Doctor of Chemical Sciences, Professor, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry (Novosibirsk, Russian Federation).
The defense will take place on August 27, 2026, at 10:00 AM in the Dissertation Council for the training direction «8D053 – Physical and chemical sciences» in the specialty «8D05306 – Chemistry» of L.N. Gumilyov Eurasian National University. The Dissertation Council meeting will be held offline and online.
Link: https://clck.ru/3UQDQs
Address: K. Satpayev Street, 2, Room: 302, Astana, Republic of Kazakhstan.
Abstract (English): ABSTRACT of the dissertation submitted for the degree of Doctor of Philosophy (PhD) in the educational program “8D05306 – Chemistry” by Turgunbayeva Aiman Akylkyzy “Chemical composition and biological activity of some extracts and metabolites of Rheum tataricum L.fil” General Characteristics of the Work. This dissertation is devoted to the investigation of the chemical composition of biologically active compounds (BACs) of the Rheum tataricum L.fil. (Polygonaceae) their isolation, and the elucidation of their structures using chemical methods (acid hydrolysis, acylation, methylation) and physicochemical analytical techniques (IR, UV, 1H and 13C NMR spectroscopy, 2D NMR–HMBC, mass spectrometry, elemental analysis, and X-ray crystallographic analysis). The antitumor, cytotoxic, and antioxidant activities of the extracts and individual compounds isolated from the studied plant were also examined. Relevance of the Research Topic The relevance of this research is determined by contemporary trends in the fields of bioorganic chemistry and the chemistry of natural compounds, which are focused on the study of biologically active substances of natural origin with the aim of further developing highly effective, safe, and economically accessible pharmaceuticals based on them. The growing global demand for plant-derived medicinal products stimulates the intensive development of phytochemical research and the systematic search for new substances with pronounced pharmacological activity. This trend is driven by the need to reduce the adverse effects of synthetic drugs and to ensure the rational, scientifically grounded application of natural compounds possessing high therapeutic potential. The Republic of Kazakhstan possesses significant reserves of renewable plant resources, the rational utilization of which creates opportunities for the development of the domestic pharmaceutical industry, reduction of import dependence, and expansion of the range of phytopharmaceutical products. Degree of development of the research topic. Plants of the genus Rheum represent a promising source of valuable biologically active compounds. This genus includes more than 60 species, 9 of which are described in the flora of Kazakhstan. Representatives of this genus are widely distributed across regions of Asia and Europe and are used both as food plants and in traditional medicine. In folk medicine, plants of the genus Rheum are employed as anti-inflammatory, laxative, and antimicrobial agents, and are also used in the treatment of diseases of the liver, kidneys, and gastrointestinal tract. Phytochemical studies conducted by both international and domestic researchers indicate the presence in plants of the genus Rheum of anthracene derivatives, flavonoids, phenolic glycosides, stilbenes, lignans, tannins, and carbohydrates. In samples of Rheum tataricum L. growing in the desert regions of the Republic of Kazakhstan, flavonoids, catechins, tannins, and other phenolic compounds have been identified, indicating the high pharmacological potential of this plant. Thus, a comprehensive investigation of the chemical composition of Rheum tataricum L.fil., including the isolation of biologically active compounds and the evaluation of their pharmacological properties, provides a scientific basis for the development of new medicinal products of natural origin. Objective of the Study: To investigate the chemical composition of biologically active compounds of Rheum tataricum L.fil. and to evaluate their pharmacological activity. Research Tasks: – to perform a comparative phytochemical analysis of the main groups of biologically active compounds in the aerial and underground parts of Rheum tataricum L.fil.; – to determine the chemical composition of lipophilic metabolites in the aerial and underground parts of Rheum tataricum L.fil.; – to develop an optimized technological scheme for the isolation of a complex of biologically active compounds, followed by the isolation of individual components from Rheum tataricum L.fil.; – to elucidate the structures of the isolated individual compounds using chemical methods and modern physicochemical techniques; – to determine the biological activity of the isolated extracts and individual compounds. Research Methods: In the dissertation research, the following chemical methods were employed: hydrolysis, acylation, and methylation. The physicochemical methods used included IR and UV spectroscopy, 1H and 13C NMR spectroscopy, 2D NMR (HMBC), mass spectrometry, high-performance liquid chromatography (HPLC), gas chromatography–mass spectrometry (GC–MS), as well as elemental and X-ray crystallographic analysis (XRD). The determination of biological activity (in vitro) was carried out using the MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide), as well as the ferric reducing antioxidant power assay (FRAP). Objects of Study: The aerial and underground parts of Rheum tataricum L.fil., growing in the vicinity of the Zailiysky Alatau in the Almaty Region of the Republic of Kazakhstan, collected during the budding stage. Subject of Study: Determination of the qualitative characteristics and component composition of Rheum tataricum L.fil.; development of an optimal technological scheme for the isolation of biologically active compounds from various extracts; structural elucidation of the isolated compounds using chemical and physicochemical methods; and evaluation of the biological activity of the extracts and individual compounds. Main Research Results and Justification of Novelty: Within the framework of this study, for the first time, a comparative phytochemical investigation (qualitative and quantitative composition) of the aerial and underground parts of Rheum tataricum L.fil., growing in the vicinity of the Zailiysky Alatau, was carried out. 1. Using GC–MS analysis of chloroform and hexane extracts of Rheum tataricum L.fil., 24 compounds were identified in the aerial part of the plant, including 9 alkane derivatives, 4 fatty acids and their derivatives, 3 terpenes, 4 steroids, 3 phenolic compounds, and 1 simple ether. In the underground part, 12 compounds were identified, including 1 alkanol, 6 steroids, 4 phenolic derivatives, and 1 sesquiterpenoid. For the first time, 7 compounds were detected for the genus Rheum and 19 compounds for the species Rheum tataricum L.fil. 2. A rational technological scheme for the isolation of a complex of biologically active compounds from the roots of Rheum tataricum L.fil. was developed. As a result, 10 phenolic compounds were isolated, including 1 phenol, 4 phenolic glycosides, 1 phenolic acid, 3 stilbenes, and 1 gallotannin. Additionally, five derivatives of phenolic compounds were obtained through chemical modification. 3. For the first time for the genus Rheum, six compounds were isolated and identified: 3,5-di-O-caffeoylquinic acid (14); 5-caffeoyl-3-O-(p-coumaroyl)quinic acid (15); peracetate derivatives of (R)- and (S)-rhododendrin (16a–17a); (R)-4-(4-hydroxyphenyl)-2-butanol – (-)-rhododendrol (18); and methyl 3,4,5-trimethoxybenzoate (25). 4. For the first time in Rheum tataricum L.fil., seven compounds were isolated and identified, including: 1-O-galloyl-β-D-glucopyranose (β-glucogallin) (13); (R)-4-(4-hydroxyphenyl)-2-butanol-2-β-D-glucopyranoside (rhododendrin) (16); (S)-4-(4-hydroxyphenyl)-2-butanol-2-β-D-glucopyranoside (epi-rhododendrin) (17); (S)-4-(4-hydroxyphenyl)-2-butanol – (+)-rhododendrol (19); 4-(4-hydroxyphenyl)-butan-2-one (raspberry ketone) (20); 3,3′,5-trihydroxy-4′-methoxystilbene-3-O-β-D-glucopyranoside (raponticin) (21); and 3,5-dihydroxy-4′-methoxystilbene-3-O-β-D-glucopyranoside (deoxyraponticin) (22). 5. For the first time, the antitumor activity (in vitro) of ethanol, MTBE, and ethyl acetate extracts, as well as isolated compounds (13, 16, 16a–17a, 18, 20, 22, 23), was investigated on the following cancer cell lines: cervical cancer C-33A (cervical carcinoma independent of human papillomavirus), HPV-associated cervical cancer CaSki (genotype 16), HeLa (genotype 18), breast adenocarcinoma MCF-7, prostate cancer DU-145, and glioblastoma (T98G and SNB-19). Metabolites 16 and 18 exhibited high cytotoxic activity against CaSki and MCF-7 cell lines. Compounds 22 and 23 showed the greatest cytotoxicity toward MCF-7 breast adenocarcinoma cells. In the SNB-19 glioblastoma cell line, the cytotoxic activity of resveratroloside (23) was comparable to that of doxorubicin. Based on the evaluation of acute toxicity on normal gastric epithelial VERO cells, the tested extracts and metabolites exhibited no toxic effects. Both ethanol and ethyl acetate extracts demonstrated high antioxidant activity. Statements Submitted for Defense: 1. On the basis of a comparative phytochemical analysis of the aerial and underground parts of Rheum tataricum L. fil., biologically active substances were identified polyphenols (tannins, phenols, and phenolic acids), which predominate in terms of quantitative content in the roots of the studied species. 2. It was established that the chloroform and hexane extracts of Rheum tataricum L. fil. differ in the composition of lipophilic metabolites. Using GC–MS analysis, 24 compounds were identified in the aerial part and 12 compounds in the underground part. 3. A technological scheme for the sequential extraction of biologically active substances from the roots of Rheum tataricum L. fil. using organic solvents of increasing polarity (hexane, chloroform, methyl-tert-butyl ether, ethyl acetate) was developed, which is optimal for obtaining the maximum yield of target compounds and their subsequent isolation in individual form using chromatographic methods. 4. From the roots of Rheum tataricum L. fil., 13 phenolic compounds were isolated, including 6 new compounds for the genus Rheum, the structures of which were determined using a combination of chemical (acid hydrolysis, acylation, methylation) and physicochemical (IR, UV, ¹H and ¹³C NMR, 2D NMR–HMBC, mass spectrometry, elemental analysis, and X-ray structural analysis) methods. 5. It was established that the investigated extracts and phenolic compounds isolated from the roots of Rheum tataricum L.fil. exhibit biological activity against the tumor cell lines CaSki, MCF-7, and SNB-19, while showing no toxic effect on the VERO epithelial cell line. Rhododendrin (16), (−)-rhododendrol (18), desoxyrhaponticin (22), and resveratroloside (23) demonstrated pronounced cytotoxic activity. The ethanolic and ethyl acetate extracts, within the concentration range of 0.25–1 mg/ml, exhibited stronger antioxidant activity than the reference standard, ascorbic acid. Practical Significance of the Work: As a result of this work, the plant Rheum tataricum L.fil., growing in Kazakhstan, has been identified and proposed as a promising source of biologically active compounds. According to official data from the Ministry of Health of the Republic of Kazakhstan, published on the portal Kursiv.media, in 2024 breast cancer ranked first among oncological diseases in the country, while cervical cancer remains one of the most common cancers among women. In this regard, considering the high antitumor activity of the isolated compounds against cancer cells, as well as the substantial natural resources of plant raw materials available in the Republic of Kazakhstan, further in-depth investigation of these compounds appears warranted with a view to their potential medical application. Theoretical Significance of the Work: The theoretical significance of the dissertation lies in the scientific justification for the development of an optimal method for the isolation of phenolic compounds from Rheum tataricum L.fil. The obtained results contribute to the advancement of the chemistry of natural compounds, provide a foundation for further fundamental research in this field, and help expand scientific understanding of the phytochemical potential of plants in the genus Rheum. Author’s Personal Contribution: The author personally carried out the experimental part of the dissertation, including the processing, analysis, interpretation, and discussion of the obtained scientific results. Publications based on the work have been prepared in domestic and international scientific journals. In addition, the author actively participated in the formulation of research objectives, discussion of results, and their practical implementation, working closely with the scientific supervisors. Dissertation Approval and Presentation: The main results of the dissertation research were presented at the XII International Birimzhanov Congress on Chemistry and Chemical Technology (December 4–6, 2024, Almaty) and at the conference “Chemistry and Technology of Plant Substances: Abstracts of the XIII International Scientific Conference with a School of Young Scientists” (2024, Syktyvkar). Publications: The results of the dissertation are presented in one article published in a peer-reviewed journal indexed in Scopus and Web of Science, and in two articles in national specialized journals included in the second list recommended by the Committee for Control in the Sphere of Education and Science of the Ministry of Education and Science of the Republic of Kazakhstan. In 2025, one article was published in the international scientific journal Molecules. According to Journal Citation Reports (Clarivate), the journal has a Journal Impact Factor of 4.6 and belongs to the second quartile (Q2; 68.4%) in the category “Chemistry, Multidisciplinary.” In the Scopus database, the journal is ranked in the first quartile (Q1; 87%) in the field of “Organic Chemistry.” The doctoral student actively participated in conducting experiments, interpreting the obtained results, and preparing and formatting scientific manuscripts. The doctoral student is the first author of the published papers. 1. Turgunbayeva A.A., Sultanova N.A., Hamad M.S., Savelyev V.A., Chernyak E.I., Bagryanskaya I.Y., Pokrovsky M.A., Pokrovsky A.G., Gemejiyeva N.G., Shults E.E. Isolation and identification of secondary metabolites in Rheum tataricum L.fil. growing in Kazakhstan and surveying of its anticancer potential // Molecules. – 2025. – Vol. 30. – № 14. – Art. 2978. 2. Turgunbayeva A.A., Shults E.E., Salnikova O.I., Savelyev V.A., Gemejiyeva N.G., Sultanova N.A., Zhatkanbaev E.E., Zhatkanbayeva Zh.K. Study of lipophilic components of Rheum tataricum L.f. // Kazakhstan Chemical Journal. – 2025. – № 3 (91). – P. 44–52. 3. Turgunbayeva A., Gemejiyeva N., Sultanova N. Study of the chemical composition of the chloroform extract of Rheum tataricum L.f. using gas chromatography // Academic Scientific Journal of Chemistry. – 2025. – Vol. 3. – № 464. – P. 274–284. Structure of the Dissertation: The dissertation comprises 119 pages and is structured into an introduction, three main sections, and a conclusion. The work includes 14 tables, 32 figures, and a list of 208 references.
Conclusion of the Research Ethics Committee
Defense of the dissertation: https://youtu.be/pSGIsnnv6rE?si=cbE7lesbb69W3ehV
