Nghiên cứu thành phần hóa học và hoạt tính gây độc tế bào ung thư cây đại bi blumea balsamifera (l ) DC và cây ngải cứu artemisia vulgaris l thuộc họ cúc asteraceae TT TIENG ANH

MINISTRY OF EDUCATION VIETNAM ACADEMY AND TRAINING OF SCIENCE AND TECHNOLOGY GRADUATE UNIVERSITY SCIENCE AND TECHNOLOGY LE THI THUY HANG RESEARCH CHEMICAL COMPOSITION AND BIOLOGICAL ACTIVITY OF GREAT COMPASSION TREE - BLUMEA BALSAMIFERA (L.) DC AND WORMWOOD - ARTEMISIA VULGARIS L BELONGS TO THE ASTERACEAE ASTERACEAE FAMILY Major: Organic chemistry Code: 44 0114 SUMMARY OF CHEMISTRY DOCTORAL THESIS HA NOI, 2021 The work was completed at: Institute of Science and Technology Vietnam Academy of Science and Technology Science instructor 1: Dr Nguyen Van Thanh Science instructor 2: Dr Nguyen Xuan Cuong Reviewer 1: Reviewer 2: Reviewer 3: The dissertation will be defended before the Board dots doctoral thesis Academy level, meeting at the Institute of Science and Technology Vietnam Academy of Science and Technology at the time date 2020 The thesis can be found at: - Library of Science and Technology Institute, Vietnam Academy of Science and Technology - National Library of Vietnam INTRODUCTION Medicinal plants in our country are very plentiful and diverse The use of that precious resource to prevent, cure and improve human health has a history of thousands of years and has become increasingly important Particularly herbs, according to statistics of the World Health Organization the number is up to more than 35,000 species Along with the very rapid development of modern medicine, the trend in the world to use natural herbal medicine is increasing Many secondary plant compounds of medicinal value have been isolated and put to use for therapeutic purposes According to estimates, Vietnam has about 12,000 species of vascular plants, of which about 4,000 species are used as medicine The trend of going deep into traditional medicine verification research and searching for natural compounds with high biological activity to make medicine from medicinal herbs has been increasingly concerned by the world Blumea balsamifera (L.) DC and wormwood - Artemisia vulgaris L are two medicinal plants of the Asteraceae family, widely used in traditional medicine in Vietnam and other countries in the region, currently being interested by scientists around the world assist Many active ingredients have been discovered from the cannabis plant such as blumealactone A, blumealactone B, blumealactone C exhibiting cytotoxic activity sarcoma, compounds (2R, 3S) - (-) - 4′-Omethyldihydroquercetin The ability to fight gout has a strong inhibitory effect on the enzyme xanthine oxidase Wormwood extract A vulgaris has been reported to have cytotoxic activity on the breast cancer cell line MCF-7, gastric cancer cells AGS and cervical cancer cells HeLa However, at present, these two Vietnamese herbs have not been studied much in terms of chemistry and biological activity Therefore, the thesis "Research on chemical constituents and cytotoxic activity of Blumea balsamifera (L.) DC" and Artemisia vulgaris L belonging to the family – Asteraceae” to focus on the chemical composition and biological activity of the marbles - B balsamifera (L.) DC and wormwood - A vulgaris L The research results of the thesis will create a scientific basis for the next applied research of these medicinal plants in Vietnam The content of the thesis includes: Isolation of compounds from the rhubarb - Blumea balsamifera (L.) DC and wormwood - Artemisia vulgaris L by chromatography Determination of the chemical structure of compounds isolated by physical and chemical methods Evaluation of cytotoxic activity of compounds isolated The layout of the thesis: The thesis consists of 130 pages with 28 tables, 78 pictures and 106 references The thesis includes chapters: Introduction (3 pages), Chapter 1: Overview (27 pages); Chapter 2: Subject and research method (19 pages); Chapter 3: Results and discussion (65 pages); The novelty of the thesis (1 page); Conclusion (1 page); Recommendations (1 page); Articles related to the thesis (1 page); References (12 pages); Appendix (83 pages) CHAPTER OVERVIEW Includes an overview of domestic and international researches on chemical constituents and biological activit of compassion tree - B balsamifera (L.) DC and wormwood tree - A vulgaris L 1.1 Researches on compassion trees - B balsamifera (L.) DC 1.1.1 Research in the country Only one study of the chemical constituents with pure compounds isolated as bioactive plant compassion published in 2012 1.1.2 Research around the world Studies from 1981 up to now show that there are more than 76 pure compounds isolated from compassion plant with main groups of substances as flavone and terpene Including 34 flavone compounds and 42 terpene compounds In the group of terpene compounds, most of them are sesquiterpenes 1.1.3 Researches on the biological activity of B balsamifera (L.) DC Several compounds have been isolated from compassion plant compassion The crude extract of this plant showed cytotoxicity cancer cells, the ability antioxidant, antibacterial activity and a number of other properties such as anti-trust for the liver, against obesity, diabetes, blood pressure 1.2 Researches on wormwood trees - A vulgaris L 1.2.1 Research in the country Only research on chemical composition with 43 pure terpenes was published in 2004 1.2.2 Research around the world Studies from 1966 to date show that more than 42 compounds were isolated from the plant with the group of flavones and terpene mainly In which there are 30 flavones and the rest are terpene compounds In the group of terpene compounds, the main part is monoterpene and sesquiterpene 1.1.3 Studies of the biological activity of wormwood tree - A vulgaris Research on wormwood extract shows cancer cytotoxicity, antioxidant properties and several other activities such as diabetes, blood pressure, intestinal and respiratory disorders, and anti-toxic effects liver, resistance to malaria, resistance to infertility CHAPTER SUBJECTS AND METHODOLOGY 2.1 Plant sample Sample of compassion trees - B balsamifera was collected in Vinh Phuc in May 2016 and by TS Nguyen The Cuong, Institute of Ecology and Biological Resources Template (TPCN-22) was kept at the Institute of Marine Biochemistry and Institute of Ecology and Biological Resources Sample of wormwood trees - A vulgaris L was collected at Bach Tu Liem, Hanoi in March 2016 and by TS Nguyen The Cuong, Institute of Ecology and Biological Resources Template (TPCN-07) was kept at the Institute of Marine Biochemistry and Institute of Ecology and Biological Resources 2.2 Methods of isolation of compounds Use chromatographic methods 2.3 Structure determination method Using modern spectroscopy methods such as one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy, high resolution mass spectrometry (HR-ESI-MS), circular dichromatic spectroscopy (CD) 2.4 Method of determining biological activity Try cytotoxic activity by SRB method 2.5 Experiment: 2.5.1 Isolation of compounds from the compassion tree – B balsamifera (L.) DC Figure 2.1: Extraction diagram of compassion trees Figure 2.2: Diagram isolated substances from plant extracts water compassion Figure 2.3: Diagram of isolating substance from Dregs dichloromethane 2.5.2 Isolation of compounds from the wormwood trees – A vulgaris L Figure 2.4: Extraction diagram of wormwood trees Figure 2.5: Diagram isolated substances from water extracts of wormwood plant 2.5.3 Spectral data for new compounds Compound BB1: White amorphous powder Molecular formula C16H21NaO10S (M = 428) HR-ESI-MS: m/z 451,0644 [M+Na]+ (Theoretical calculation for cation C16H21Na2O10S+ 451,0640) H-NMR (500MHz, CD3OD) δH ppm: 3.35 (2H, m, H-7), 5.06 (2H, m, H-9), 5.97 (1H, m, H-8); 4.98 (1H, d, J = 8.0 Hz, H-1’), 6.74 (1H, dd, J = 8.0; 2.0 Hz, H-5); 6.84 (1H, d, J = 2.0 Hz, H-3), 7.11 (1H, d, J = 8.0 Hz, H-6), 3.73 (1H, dd, J = 12.0; 5.5, H1-6’), 3.88 (1H, dd, J =12.0; 2,0 Hz, H2-6’), 3.65 (1H, t, J = 9.0, H-4’), 3.69 (1H, dd, J =9.0, 8.0 Hz, H-2’), 3.47 (1H, m, H-5’), 4.36 (1H, t, J = 9.0 Hz, H-3’), 3.85 (s, OCH3) 13 C-NMR (125MHz, CD3OD) δC ppm: 146.30 (C-1), 150.97 (C-2), 114.42 (C-3), 136.61 (C-4), 122.08 (C-5), 118.56 (C-6), 40.74 (C-7), 138.99 (C-8), 115.84 (C-9), 102.76 (C-1'), 73.54 (C-2'), 85.32 (C-3'), 70.15 (C-2'), 77.68 (C-5'), 62.28 (C-6'), 56.79 (OCH3) Compound BB2: White amorphous powder Molecular formula C16H27O9NaS (M = 418) HR-ESI-MS: m/z 441,1167 [M + Na]+ (Theoretical calculation for cation [C16H27Na2O9S]+ 441,1166) H-NMR (500MHz, CD3OD) δH ppm: 4,37 (1H, d, J = 8,0 Hz, H-1’), 3,37 (1H, dd, J = 9,0; 8,0 Hz, H-2’), 4,25 (1H, t, J = 9,0 Hz, H-3’), 3,55 (1H, t, J = 9,0 Hz H-4’), 3,30 (1H, m, H-5’), 3,71 (1H, dd, J = 12,0; 5,5 Hz, H1-6’), 3,87 (1H, dd, J = 12,0; 2,0 Hz, H2-6’), 4,17 (1H, ddd, J = 3,0; 2,0; 9,0 Hz, H-2), 1,22 (2H, m, H1-3, H1-6), 2,19 (1H, ddd, J = 1,5; 5,0; 9,5, H2-3), 1,63 (1H, br t, J = 4,5 Hz, H-4), 1,31 (1H, ddd, J = 4,5; 9,5; 13,5 Hz, H1-5), 1,73 (1H, m, H2-5), 2,13 (1H, ddd, J = 4,5; 9,5, 13,5 Hz, H2-6), 0,89 (6H, s, H-8, H-9), 0,91 (3H, s, H-10) 13 C-NMR (125MHz, CD3OD) δC ppm: 50,04 (C-1), 84,61 (C-2), 36,64 (C-3), 46,35 (C-4), 29,00 (C-5), 27,68 (C-6), 49,00 (C-7), 20,24 (C-8), 19,30 (C-9), 13,92 (C-10), 102,91 (C-1'), 73,76 (C-2'), 85,87 (C-3'), 70,45 (C-4'), 77,38 (C-5’), 62,59 (C-6’) Compound BB3: Colorless oil Molecular formula C20H32O7 (M 384) HR-ESI-MS: m/z 407,2046 [M+Na]+ (Theoretical calculation for cation [C20H32NaO7]+ 407,2040) H-NMR (500MHz, CD3OD) δH ppm: 2,25 (1H, dt, J = 17,0, 2,0 Hz, H1-2), 2,96 (1H, dd, J = 2,0; 17,0 Hz, H2-2), 5,45 (1H, br s, H-3), 3,02 (1H, br s, H-5), 1,80 (1H, m, H-7), 1,81 (1H, m, H1-8), 2,18 (1H, m, H2-8), 4,77 (1H, dd, J = 11,0; 6,5 Hz, H-9 ), 1,95 (1H, m, H-11), 1,06 (3H, d, J = 7,0 Hz, H-12), 0,98 (3H, s, H-13), 1,25 (3H, s, H-14), 1,84 (3H, s, H-15), 3,88 (1H, q, J = 6,5 Hz, H-18), 1,20 (3H, d, J = 6,5 Hz, H-19); 1,36 (3H, s, H-20), 13 C-NMR (125MHz, CD3OD) δC ppm: 93,02 (C-1), 47,00 (C-2), 126,55 (C-3), 138,08 (C-4), 64,86 (C-5), 107,30 (C-6), 51,69 (C-7), 27,52 (C-8), 80,02 (C-9), 81,30 (C-10), 29,11 (C-11), 23,38 (C-12), 19,44 (C-13), 19,70 (C-14), 17,16 (C-15), 176,53 (C-16), 78,83 (C17), 72,95(C-18), 17,02 (C-19), 22,75 (C-20) Compound AV1: Colorless oil Molecular formula C15H20O5 (M = 280).HR-ESI-MS: m/z 281,1386 [M+H]+, Theoretical calculation for cation [C15H21O5]+ 281,13835 H-NMR (500MHz, CDCl3) δH ppm: 5,85 (t, J = 2,0Hz, H-2), 4,18 (dd, J = 2,0, 1,0 Hz, H-3), 3,20 (dt, J =11,5, 1,5 Hz, H-5), 4,07 (dd, J = 11,5, 9,5 Hz, H-6), 3,35 (m, H-7), 1,49-2,25 (m, 4H, H-8, H-9), 5,54 (d, J = 3,0 Hz, H1-13), 6,10 (d, J = 3,0, H2-13), 1,45 (3H, s, H-14), 1,40 (3H, s, H-15) 13 C-NMR (125MHz, CDCl3) δC ppm: 152,5 (C-1), 129,2 (C-2), 81,1 (C-3), 80,4 (C-4), 59,6 (C-5), 83,6 (C-6), 46,6 (C-7), 24,5 (C-8), 39,1 (C-9), 73,1 (C-10), 141,9 (C-11), 172,3 (C-12), 119,2 (C-13), 31,2 (C14), 22,5 (C-15) Compound AV2: Colorless oil Molecular formula C15H20O5 (M = 280) HR-ESI-MS: m/z 281,1388 [M + H]+, Theoretical calculation for cation [C15H21O5]+ 281,13835 H-NMR (500MHz, CD3OD) δH ppm: 5,79 (s, H-2), 4,41 (s, H-3), 3,04 (d, J =10,5 Hz, H-5), 4,14 (t, J = 10,5 Hz, H-6), 3,37 (m, H-7), 1,531,99 (m, 4H, H-8, H-9), 5,54 (d, J = 3,0 Hz, H1-13), 6,11 (d, J = 3,0, H2-13), 1,46 (3H, s, H-14), 1,37 (3H, s, H-15) 10 The1H-NMR and 13C-NMR spectra of BB1 showed the signals of a 1,2,4 trisubstituted aromatic ring [C 146.30 (C-1), 150.97 (C-2), 114.42 (C-3), 136.61 (C-4), 122.08 (C-5) and 118.56 (C-6); H 6.84 (1H, d, J = 2.0 Hz, H-3), 6,74 (1H, dd, J = 2.0, 8.0 Hz, H-5) and 7.11 (1H, d, J = 8.0 Hz, H-6)], a methylene group [C 40.74 (C-7); H 3,35 (2H, m, H-7)], a monosubstituted double bond [C 138.99 (C-8) and 115.84 (C-9); H 5.97 (1H, m, H-8) and 5.06 (2H, m, H-9)] and a methoxy group [C 56.79 (OMe); 3.85 (3H, s, OMe)], indicating that this compound is a derivative of eugenol Figure 3.1.1.c 1H-NMR spectrum of BB1 Figure 3.1.1.d 13C-NMR spectrum of BB1 Table 3.1.1: NMR spectral data of compound BB1 11 δHa,c mult (J= Hz) 146.30 C 150.97 C 114.42 CH 6.84 d (2.0) 136.61 C 122.08 CH 6.74 dd (2.0, 8.0) 118.56 CH 7.11 d (8.0) 40.74 CH2 3.35 m 138.99 CH 5.97 m 115.84 CH2 5.06 m 1' 102.76 CH 4.98 d (8.0) 2' 73.54 CH 3.69 dd (8.0, 9.0) 85.32 CH 4.36 t (9.0) 3' 70.15 CH 3.65 t (9.0) 4' 77.68 CH 3.47 m 5' 6' 62.28 CH2 3.73 dd (5.5, 12.0) 3.88 dd (2.0, 12.0) 2-OCH3 56.79 CH3 3.85 s measure in CD3OD, b125MHz, c 500MHz C a δCa,b DEPT HMBC (HC) 1, 2, 5, 1, 3, 1, 2, 3, 4, 5, 8, 7 Figure 3.1.1.e HSQC spectrum of BB1 12 In addition, the signals of a hexose were also recorded at C 102.76 (C-1), 73.54 (C-2), 85.32 (C-3), 70.15 (C-4), 77.68 (C-5) and 62.28 (C-6)/H 4.98 (1H, d, J = 8.0 Hz, H-1), 3.69 (1H, dd, J = 8.0, 9.0 Hz, H-2), 4.36 (1H, t, J = 9.0 Hz, H-3), 3.65 (1H, t, J = 9.0 Hz, H-4), 3,47 (1H, m, H-5), 3,73 (1H, dd, J = 5.5, 12.0 Hz, Ha-6) and 3.88 (1H, dd, J = 2.0, 12.0 Hz, Hb-6) From the above data, 1HNMR and 13C-NMR spectral data of BB1 were compared and showed compliance with corresponding published values for the eugenyl O-βD-glucopyranoside [83] (see table 3.1.1), except big difference in the signals of the sugar unit The 13C-NMR signal at C-3’ of BB1 was strongly shifted towards the low field region at C 85.32 compared with the corresponding signal of eugenyl O-β-D-glucopyranoside at C 79.0, showing that the bonding position of the sulphate at this carbon as in the case of the compound ptilosaponoside B with the C-3’ signal appearing at C 85.8 The binding position of the (3-O-sodium sulfo)glucopyranose unit at C-1 was demonstrated by the HMBC cross-peak of the anomeric proton H-1’ (H 4.98) with carbon C-1 (C 146.3) The detailed analysis of other HMBC interactions (see figure 3.1.1.a) allows to prove the exact chemical structure of BB1 as eugenyl 1-O-β-D-(3-O-sodium sulfo)glucopyranoside This is a new compound and named balsamiferoside A Figure 3.1.1.f HMBC spectrum of BB1 3.1.2 The compounds isolated from compassion trees – B 13 balsamifera (L.) DC From the parts of the giant marbles (stem, branches, leaves) using a combination of chromatographic methods, compounds were isolated, including monoterpene compounds, sesquiterpene compounds, flavonoid compounds and phenolic glycoside compounds Among them, there are new substances balsamiferoside A (BB1), balsamiferoside B (BB2) and balsamiferine K (BB3), compounds (BB4BB8) isolated from the rhizobarb tree for the first time Chemical structures of the compounds were determined based on analysis of nuclear magnetic resonance spectroscopy data (1H-NMR, 13 C-NMR, HSQC, HMBC, COSY, NOESY); High resolution mass spectrometry (HR-ESI-MS) as well as comparison with the published data BB1 (Hợp chất mới) BB2 (Hợp chất mới) BB3 (Hợp chất mới) BB6 BB4 BB7 BB5 BB8 BB9 The chemical structure of compounds isolated from compassion trees – B balsamifera (L.) DC 14 3.2 Determination of the structure of compounds isolated from wormwood – A vulgaris L 3.2.1 Compound AV1: Vulgarolide A (Compound new) Compound AV1 are isolated as a colorless oil The molecular formula was determined to be C15H20O5 by the appearance of the pseudo-molecular ion peak [M + H]+ at m/z 281,13868 on the high resolution mass spectrum HR-ESI-MS (theory calculation for cation [C15H21O5]+ is 281,13835) Its NMR spectral data is indicative for a sesquiterpene lactone, a major class of the Artemisia species [95] Figure 3.2.1.a Chemical structure of the compound AV1 Figure 3.2.1.b HR-ESI-MS spectrum of compound AV1 15 Figure 3.2.1.c 1H-NMR spectrum of AV1 C Figure 3.2.1.d 13C-NMR spectrum of AV1 Table 3.2.1 1H and 13C-NMR data of compound AV1 DEPT H (J = Hz) C HBMC (H C) 152,5 C 129,2 CH 5,85 (t, 2,0) C-10 81,1 CH 4,18 (dd, 2,0; 1,0) 16 80,4 59,6 83,6 46,6 C CH CH CH 24,5 CH2 39,1 CH2 10 11 12 73,1 141,9 172,3 C C C 13 119,2 CH2 14 15 31,2 22,5 CH3 CH3 3,20 (dt, 11,5; 1,5) 4,07 (dd, 11,5; 9,5) 3,31 (m) 1,51 (m) 2,24 (m) 1,75 (m) 1,99 (m) 5,54 (d, 3,0) 6,10 (d, 3,0) 1,45 (s) 1,40 (s) C-7; C-11; C-12 C-1; C-9; C-10 C-3; C-4; C-5 C: of AV1 measured 125MHz in CD3OD # Figure 3.2.1.e HSQC spectrum of AV1 17 Figure 3.2.1.f HMBC spectrum of AV1 On the 1H and 13C NMR spectra of AV1 revealed characteristic signals of a trisubstituted double bond [C 152.5 (C, C-1) and 129.2 (CH, C-2)/H 5.85 (1H, t, J = 2.0 Hz, H-2)], a terminal disubstituted double bond [C 141.9 (C, C-11) and 119.2 (CH2, C-13)/H 5.54 and 6.10, H-13, each 1H, d, J = 3.0 Hz], two oxymethine groups [C 81.1 (C-3) and 83.6 (C-6)/H 4.18 (1H, dd, J = 2.0, 1.0 Hz, H-3) and 4.07 (1H, dd, J = 11.5, 9.5 Hz, H-6)], the two oxygenated quaternary carbon [C 80,4 (C-4) and 73,1 (C-10)], a lactone carbonyl carbon [C 172,3 (C-12)] and singlet methyl groups [C 31,2 (C-14) and 22,5 (C-15)/H 1,45 (H-14) and 1,40 (H-15), each 3H, s] The remaining signals belong to methine groups [C 59.6 (C-5) and 46.6 (C-7)/H 3.20 (1H, dt, J = 11.5, 1.5 Hz, H-5) and 3.31 (1H, m, H-7)] and methylene groups [C 24.5 (C-8) and 39.1 (C-9)/H 1.51 (1H, m, Ha-8), 2.24 (1H, m, Hb-8), 1.75 (1H, m, Ha-9) and 1.99 (1H, m, Hb-9)] 18 Figure 3.2.1.g COSY spectrum of AV1 Figure 3.2.1.h NOESY spectrum of AV1 19 Figure 3.2.1.i The main COSY( ), HMBC ( NOESY ( ) interactions of AV1 ) and Figure 3.2.1.j Circular dichroism (CD) spectrum of AV1 Detailed analysis of interactions on the COSY spectrum allows connectivities of H-2/ H-3 and H-5/H-6/H-7/H2-8/H2-9 This data, along with HMBC cross-peaks of H-2 with C-10; H-13 with C7, C-11 and C-12; H-14 with C-1, C-9 and C-10; and of H-15 with C3, C-4 and C-5; allows to accurately determine the planar structure of AV1 (figure 3.2.1.i) The configurations of the lactone ring were assigned by CD spectrum with a negative Cotton effect at 252 nm consistent with the nπ* transition of the α-methylene γ-1actone chromophore In addition, the agreement of 1H and 13C NMR spectral data at positions C-3, C-4 and C-15 with corresponding data of 3, 4,10 -trihydroxy-11H-guai-1-en-12,6-olide, 3,4,10 - 20 trihydroxy-8-acetoxyguai-1,11(13)-dien-6, 12-olide and data at C10 and C-14 with those of 3,4- -epoxy-8-deoxycumambrin B, suggesting  configuration of all hydroxy groups at C-3, C- 4, and C10 This was further confirmed by the NOESY spectrum with the interactions of H-15 with H-3 and H-6 and that of H-6 with H-14 Proton H-5 has an NOESY interaction with H-7 proving that this proton has  configuration From the above analysis, the chemical structure of AV1 was elucidated to be 3,4,10-trihydroxyguai1,11(13)-diene-6,12-olide This is a new compound and named vulgarolide A 3.2.2 Compounds isolated from the wormwood plant – A vulgaris L AV1 AV2 AV5 AV3 AV4 AV6 AV7 AV8 AV9 AV10 The chemical structure of compounds from the wormwood plant – A vulgaris L 21 From the parts of wormwood tree (stem, branch, leaf) using a combination of chromatographic methods 10 compounds were isolated, including sesquiterpenes, phenolic glycosides, megastigman glycosides and lignal glycosides Among them, two compounds, vulgarolide A (AV1) and vulgarolide B (AV2), are new; compounds (AV3AV10) were first isolated from wormwood plant Chemical structures of the compounds were determined based on detailed analysis of nuclear magnetic resonance spectroscopy data (1HNMR, 13C-NMR, HSQC, HMBC, COSY, NOESY); high resolution mass spectrometry (HR-ESI-MS); circular dichroism (CD) spectrum; as well as comparison with published spectral data 3.3 Results of biological activity test 3.3.1 Test Results activity of compounds isolated from plants compassion – B balsamifera (L.) DC Results of screening for cytotoxic activity on five human cancer cell lines including: human carcinoma in the mouth - KB, human hepatocellular carcinoma - HepG2 Human breast cancer (human breast carcinoma) - MCF7, Human malignant melanoma - SKMel-2 and human prostate carcinoma - LNCaP showed that BB5 and BB9 exhibited moderate and weak inhibitory activity on the tested cell lines with IC50 values from 44.53 to 98.73M 3.3.2 Test Results activity of compounds isolated from plant wormwood – A vulgaris L Compounds isolated from wormwood plant were also tested for cytotoxic activity on above cancer cell lines However, these compounds exhibited weak activity or did not exhibit cytotoxic activity on the tested cancer cell lines (IC50 > 100 M) CONCLUSION 22 This is a study on chemical constitutents and cytotoxic activity of two plants wormwood - A vulgaris and compassion - B balsamifera growing in Vietnam Research on chemical composition - By ussing combination of chromatographic and modern spectroscopic methods have isolated and identified the chemical structure of compounds from compassion plant - B balsamifera including new compounds (BB1, BB2, BB3) and 10 compounds from wormwood plant - A vulgaris of which there are two new compounds (AV1 and AV2) - From compassion plant - B balsamifera: compounds were isolated including new compounds namely balsamiferoside A (BB1), balsamiferoside B (BB2) and balsamiferine K (BB3) and known compounds: isohemiphloin (BB4); (-)angelicoidenol [(2R,5S)-bornane2,5-diol] 2-O--D-glucopyranoside (BB5); (1S,2R,4S)-borneol -Dglucopyranoside (BB6); 1,4,7-trihydroxyeudesmane (BB7); 6,15epoxy-1,4-dihydroxyeudesmane (BB8), blumeanen J (BB9) - From plants wormwood – A vulgaris: 10 compounds were isolated including new compounds namely vulgarolide A (AV1); vulgarolide B (AV2) and known compounds: dihydrosyringin (AV3); coniferin (AV4); (3S,5R,6S,9S)-3,6,9trihydroxymegastigman-7-ene-3-O--D-glucopyranoside (AV5); (6S,9R)-roseoside (AV6); corehoionoside C (AV7); pinoresinol monoglucoside (AV8); eucommin A (AV9); syringaresinol glucoside (AV10) Research on biological activity The cytotoxic activity was assessed on cell lines: KB, HepG2, MCF7, SK-Mel-2 and LNCaP of the pure compounds isolated from wormwood plant - A vulgaris and compassion plant - B balsamifera The obtained results showed that only two compounds from compassion plant - B balsamifera, (-) - angelicoidenol 2-O- -D- 23 glucopyranoside (BB5) and blumeanen J (BB9), exhibited moderate and weak cytotoxic activity against all tested cancer cell lines REQUEST From the research results on the chemical composition and cytotoxic activity of pure compounds isolated from wormwood - A vulgaris and compassion - B balsamifera, (-) - angelicoidenol 2-O-D-glucopyranoside (BB5) and blumeanen J (BB9) exhibited moderate and weak cytotoxic activity against five studied cancer cell lines Because of the limited scope of the thesis, we have only studied on cancer cell lines without the conditions and time to study on other cancer cell lines and other activities Therefore, we propose a research direction for the pure compounds isolated from wormwood - A vulgaris and compassion - B balsamifera on other cancer cell lines as well as other activities NEW FINDINGS OF THE THESIS Successfull isolation and structure elucidation of two new compounds from wormwood tree - A vulgaris namely vulgarolide A (AV1) and vulgarolide B (AV2) and new compounds from the compassion tree - B balsamifera namely balsamiferoside A (BB1), balsamiferoside B (BB2) and balsamiferine K (BB3) Assessment of cytotoxic activity on cancer cell lines: KB, HepG2, MCF7, SK-Mel-2 and LNCaP of pure compounds isolated from wormwood and compassion plants The results showed that two compounds from the compassion plant - B balsamifera, (-) angelicoidenol 2-O--D-glucopyranoside (BB5) and blumeanen J (BB9), exhibited moderate and weak cytotoxicity on all studied cancer cell lines 24 LIST OF WORKS HAS BEEN PUBLISHED Tran Thi Hong Hanh, Le Thi Thuy Hang, Phan Thi Thanh Huong, Nguyen Quang Trung, Tran Van Cuong, Nguyen Van Thanh, Nguyen Xuan Cuong, Nguyen Hoai Nam & Chau Van Minh Two new guaiane sesquiterpene lactones from the aerial parts of Artemisia vulgari Journal of Asian Natural Products Research, 2018, 20(8), 752–756 Tran Thi Hong Hanh, Le Thi Thuy Hang, Vu Huong Giang, Nguyen Quang Trung, Nguyen Van Thanh, Tran Hong Quang, Nguyen Xuan Cuong Chemical constituents of Blumea balsamifera Phytochemistry Letters, 2021, 43, 35-39 Le Thi Thuy Hang, Tran Thi Hong Hanh, Do Hoang Anh, Pham Thi Cham, Nguyen Quang Trung, Nguyen Xuan Cuong, Nguyen Van Thanh, Nguyen Hoai Nam, Initial research into the chemical composition of wormwood – Artemisia vulgaris, Journal of Chemistry, 2017, 55(5E34), 260-263 ... from medicinal herbs has been increasingly concerned by the world Blumea balsamifera (L. ) DC and wormwood - Artemisia vulgaris L are two medicinal plants of the Asteraceae family, widely used in... and biological activity Therefore, the thesis "Research on chemical constituents and cytotoxic activity of Blumea balsamifera (L. ) DC" and Artemisia vulgaris L belonging to the family – Asteraceae? ??... chemical composition and biological activity of the marbles - B balsamifera (L. ) DC and wormwood - A vulgaris L The research results of the thesis will create a scientific basis for the next applied