Nghiên cứu thành phần hóa học và hoạt tính sinh học của quả các cây gội nước (anphanamixis polystachya), xà cừ (khaya senegalensis) và xoan (melia azedarach) thuộc họ xoan (meliaceae) ở việt namtt tiê

1 MINISTRY OF EDUCATION AND TRAINING VINH UNIVERSITY VU THI HIEN STUDY ON CHEMICAL CONSTITUENTS AND BIOLOGICAL ACTIVITY OF FRUITS OF Aphanamixis polystachya (Wall.) R.Parker, Khaya senegalensis A Juss AND Melia azedarach L BELONGING TO THE FAMILY MELIACEAE IN VIETNAM MAJOR: ORGANIC CHEMISTRY Code: 62.44.01.14 PhD THESIS SUMMARY NGHE AN - 2018 The present study has been completed at: Specialized Lab Organic Chemistry, Vinh University Supervisors: Assoc Prof Dr Vu Dinh Hoang Assoc Prof Dr Hoang Van Luu Reviewer 1: Assoc Prof Dr Trinh Thi Thuy Reviewer 2: Assoc Prof Dr Do Quang Huy Reviewer 3: Assoc Prof Dr Le Duc Giang The thesis will be defended at the High-tech buildings at Vinh University, 182 Le Duan, Vinh City, Nghe An Province, 2019 At h 00 The thesis can be found at: The National Library of Vietnam Centre for information - Library Nguyen Thuc Hao, Vinh University Preamble In recent years there are many traditional medicinal plants that are subjected to the research in experimental and clinical treatment of cancer There have discovered a number of new substances, many of which are promising substances and become lead compounds The family Meliaceae is interested in the world with a very diverse and rich chemical composition including limonoid, mono-, di-, sesqui-, and triterpenoid, coumarin, chromone, lignan and flavonoid classes especially the limonoid class near 2000 interesting structural compounds, with antifungal, antimicrobial, and insecticidal activity Many limonoid compounds exhibit antimicrobial, cytotoxic, anti-tumor and anti-HIV activity Species Aphanamixis polystachya, Khaya senegalensis and Melia azedarach belong to Vietnamese folk medicinal plants However, until now, almost no research on the chemical composition and biological activity of these plants in Vietnam has been reported This thesis is aimed to clarify the use in folk, improve the effectiveness and safety of medicinal plants, develop medicinal materials to use in a more scientific way Therefore, the study field has important theoretical and practical significance, making an important contribution to finding natural resources, economic value of Vietnam's natural medicinal resources For that reason, we have chosen the topic: "Study on chemical composition and biological activity of fruits of Anphanamixis polystachya, Khaya senegalensis and Melia azedarach belonging to family Meliaceae in Vietnam” Objects The research objects of the thesis are extracts from fruits of Anphanamixis polystachya, Khaya senegalensis and Melia azedarach in Vietnam Tasks The research tasks include: - Selecting suitable solvents to extract the existing compounds from fruits of Anphanamixis polystachya, Khaya senegalensis and Melia azedarach in Vietnam - Separating and identifying structures of the compounds isolated - Assaying biological activities of the concerned compounds Methods - Collection samples: collection, identification, cultivation for some fungi, storage and preservation dried fungi of samples at the laboratory temperature (20-30 C) Isolation of compounds by a combination of chromatographic techniques; column chromatography (CC), thin layer chromatography (TLC) with different stationary phases are silica gel, Sephadex LH-20, RP-18; high-performance liquid chromatography (HPLC) - Structure elucidation by UV, IR, mass spectrometry (MS), as well as one and 13 1 two dimensional NMR techniques ( H-NMR, C-NMR, 2D- H- H-COSY, HMBC, HSQC) - Test of anti-inflammatory and antibacterial activities and plant pathogenic antifungal activity of pure compounds New contributions of the thesis Study the chemical composition and biological activity of fruits of Anphanamixis polystachya, Khaya senegalensis, Melia azedarach in Vietnam, we have obtained some results as follows: Isolated and determined the structure compounds from fruits extract of Aphanamixis polystachya, include: - 04 limonoid compounds: dysobinin, chisocheton compound E, chisocheton compound G 6α - acetoxyepoxyazadiradione VI - 02 sterol compounds: β-sitosterol, -sitosterol-3-O--D-glucopyranoside dysobinin, chisocheton compound E, chisocheton compound G 6α acetoxyepoxyazadiradione VI were isolated for the first time Isolated and determined the structure compounds from fruits extract of Khaya senegalensis, include: - 04 limonoid compounds: seneganolide, khayanone, khayanolide B, 6-acetoxymethyl angolensate - 02 flavonoid compounds: (-)-epicatechin and quercitrin Isolated and determined the structure compounds from fruits extract of Melia azedarach, include: 01 new limonoid compound 3α,12α-diacetoxy-7α-benzoyloxy-1αhydroxytrichilinin which is called trichilinin F - 02 flavonoid compounds: apigenin and quercetin 3-O-[-L-rhamnopyranosyl(1→6)]--D-glucopyranoside) - 01 triterpenoid compound: taraxerol - 02 phenolic compounds: scopoletin and acid vanillic - 02 sterol compounds: β-sitosterol, -sitosterol-3-O--D-glucopyranoside Test of anti-inflammatory biological activity and antifungal activity that causes plant diseases Evaluate the antifungal activity of compounds isolated with C acutatum, C fragariae, C gloeosporioides, F oxysporum, B cinerea P obscurans Outline of the thesis It is displayed in a total of 112 pages with 21 tables, 19 figures, diagrams Its major sections include: Introduction (4 pages), overview (25 pages), methods and experiment (20 pages), results and discussion (69 pages), conclusion (1 pages), published works (1 page) Morever, there is an appendix with 130 spectra of the compounds CHAPTER 1: OVERVIEW The thesis has conducted a literature review content: Family Meliaceae - Introduction of common plant characteristics of species belonging to the Meliaceae family, the main chemical composition of family Meliaceae as limonoid mono-, di-, sesqui-, and triterpenoid, coumarin, chromone, lignan, flavonoid and phenolic compounds… Besides, the review also mentions the biological activity and application of the family Meliaceae in agriculture, pharmaceutical Species Aphanamixis polystachya - Introduction of botanical characteristics of Aphanamixis polystachya - The chemical composition of Aphanamixis polystachya - The biological activity of Aphanamixis polystachya Species Khaya senegalensis - Introduction of botanical characteristics of Khaya senegalensis - The chemical composition of Khaya senegalensis - The biological activity of Khaya senegalensis Species Khaya senegalensis - Introduction of botanical characteristics of Melia azedarach - The chemical composition of Melia azedarach - Biological activity of Melia azedarach CHAPTER 2: METHODS AND EXPERIMENT 2.1 Methods 2.1.1 Method of collecting samples The plant material is collected at the appropriate time of the year When fresh plant material is required for study, they are washed, stored in cool place, isolation, preservation, and fermentation They are stored at appropriate conditions for the experiment 6 2.1.2 Methods of separation Thin layer chromatography (TLC); column chromatography (CC); lash column chromatography (FC); high performance liquid chromatography (HPLC); fractional crystallization 2.1.3 Methods of identifying the component structure Using modern spectroscopic methods to demonstrate structure of obtained compound consisting of ultraviolet (UV), infrared (IR), mass spectrometry (ESI1 13 MS, HR-ESI-MS), nuclear magnetic resonance spectroscopic H-NMR, C1 NMR, DEPT and HSQC, HMBC, H- H COSY 2.1.4 Methods of bioactivity assay Test anti-inflammatory activity and plant anti-fungal activity Evaluate the antifungal activity of compounds isolated with C acutatum, C fragariae, C gloeosporioides, F oxysporum, B cinerea P obscurans 2.2 Chemicals and equipment 2.2.1 Chemicals: Solvents for extraction plant material are pure The solvents for thin layer chromatography, fast column chromatography are pure analytical (PA) 2.2.2 Equipment: Melting temperature was determined with a Yanaco MP-S3; The polarity was determined with a Jasco DIP -370 polarimeter Thin layer chromatography (TLC); column chromatography (CC); lash column chromatography (FC); high performance liquid chromatography (HPLC); ultraviolet (UV), infrared (IR), mass spectrometry (ESI-MS, HR-ESI-MS), nuclear magnetic resonance spectroscopic (NMR), optical rotation and melting points measurement; 2.3 Study on compounds from fruits of Aphanamixis polystachya 2.3.1 Collecting samples The fruits of Anphanamixis polystachya was collected at the Vu Quang National Park of Ha Tinh Province, Vietnam, in August 2013 and identified by Assoc Prof Dr Tran Huy Thai, Institute of Ecology and Biological Resources Vietnam Academy of Science and Technology A voucher specimen (DHV-2013) was deposited at the herbarium of the Department of Chemistry, Vinh University 2.3.2 Isolating substances The fruits of Anphanamixis polystachya (4.0 kg) were air-dried and powdered and soaked with methanol at room temperature for days, and the combined extracts were concentrated under reduced pressure to give deep brown syrup (290.0 g) The crude extract was suspended into water and partitioned with cloroform and butanol, successively to afford cloroform (106 g), butanol (35.0 g), respectively, after removal of the corresponding solvent 7 The chloroform soluble extracts were purified by silica gel column chromatography eluted with n-hexane and acetone gradients (100:0, 25:1, 15:1, 10:1, 7:1, 5:1) and CHCl3:CH3OH (100:0, 6:1, 3:1, 2:1, 1:1) gradients to afford fractions (F1 to F7) Fraction F1 (8.6 g) was subjected to silica gel column chromatography eluted (200 gam, 60 x cm) with n-hexane/acetone (100:0, 25:1, 15:1, 10:1, 4:1) to afford seven subfractions (F1-1 to F1-7) Subfraction F1-4 was subjected to the silica gel column chromatography eluted with n-hexane/acetone (100:0, 25:1, 15:1, 10:1, 4:1) to afford AP-5 (153 mg) Fraction F2 (2.3 g) was subjected to silica gel column chromatography eluted (200 gam, 60 x cm) with n-hexane/acetone (9:1, 6:1) to afford six subfractions (F2-1 to F2-6) Subfraction F2-6 was subjected to the Sephadex LH20 column chromatography eluted (50 gam, 60x3cm) with CH3OH:H2O to afford AP-1 (41 mg) Fraction F3 (2.7 g) was subjected to silica gel column chromatography eluted (200 gam, 60 x cm) with n-hexane/acetone (9:1, 6:1, 4:1, 1:1) to afford four subfractions (F3-1 to F3-4) Subfraction F3-2 was subjected to the phase reversal (RP -18 ) column chromatography eluted (100 gam, 60 x cm) with CH3OH:H2O to afford AP-2 (31 mg) Fraction F4 (4.7 g) was subjected to silica gel column chromatography eluted (200 gam, 60 x cm) with CHCl3:CH3OH (20:1, 10:1, 6:1, 4:1, 2:1) to afford five subfractions (F4-1 to F3-5) Subfraction F4-1 was subjected to the phase reversal (RP -18 ) column chromatography eluted (100 gam, 60 x cm) with CH3OH:H2O (19:1, 16:1) to afford AP-4 (43 mg) and AP-3 (21 mg) Fraction F5 (1.5 g) was subjected to silica gel column chromatography eluted (200 gam, 60 x cm) with CHCl3:CH3OH (9:1, 6:1) to afford AP-6 (13 mg) 2.4 Study on chemical constituents of fruits of Khaya senegalensis A Juss 2.4.1 Collecting samples The fruits of Khaya senegalensis A Juss was collected at the Nghe An Province, Vietnam, in January 2014 and identified by Assoc Prof Dr Tran Huy Thai, Institute of Ecology and Biological Resources - Vietnam Academy of Science and Technology A voucher specimen was deposited at the herbarium of the Department of Chemistry, Vinh University 2.4.2 Isolating substances The fruits of Anphanamixis polystachya (4.0 kg) were air-dried and powdered and soaked with methanol at room temperature for days, and the combined extracts were concentrated under reduced pressure to give deep brown syrup (285.0 g) The crude extract was suspended into water and partitioned with n-hexane and ethyl acetate, successively to afford n-hexane (55g), butanol (95.0 g), respectively, after removal of the corresponding solvent The ethyl acetate soluble extracts were purified by silica gel column chromatography eluted with n-hexane and acetone gradients (100:0; 50:1; 39:1; 30:1; 20:1; 15:1; 9:1; 4:1; 2:1; 1:1) to afford fractions (F1 to F7) Fraction F3 was subjected to silica gel column chromatography eluted with n-hexane/acetone (20:1; 15:1; 9:1; 2:1) to afford five subfractions (F3-1 to F3-5) Subfraction F13-3 was subjected to the silica gel column chromatography eluted with n-hexane/acetone (9:1; 4:1) to afford KS1 (15 mg) and KS3 (29 mg) Fraction F4 was subjected to silica gel column chromatography eluted with chloroform:methanol (9:1) to afford KS4 (12.5 mg) Fraction F5 was subjected to silica gel column chromatography eluted with n-hexane/acetone (15:1; 9:1; 4:1; 2:1) to afford seven subfractions (F5-1 to F5-7) Subfraction F5-2 was subjected to silica gel column chromatography eluted to afford KS5 (53 mg) Fraction F5-4 (4.7 g) was subjected to silica gel column chromatography eluted with chloroform: methanol (15:1, 9:1) to afford KS6 (71.5 mg) 9 2.5 Study on chemical constituents of fruits of Melia azedarach 2.5.1 Collecting samples The fruits of Melia azedarach was collected at the Pu Huong National Park of Nghe An Province, Vietnam, in August 2016 and identified by Assoc Prof Dr Tran Huy Thai, Institute of Ecology and Biological Resources - Vietnam Academy of Science and Technology A voucher specimen (DHV 2016) was deposited at the herbarium of the Department of Chemistry, Vinh University 2.5.2 Isolating substances The fruits of Anphanamixis polystachya (5.0 kg) were air-dried and powdered and soaked with methanol at room temperature for days, and the combined extracts were concentrated under reduced pressure to give deep brown syrup (425.0 g) The crude extract was suspended into water and partitioned with ethyl acetate and n-butanol, successively to afford chloroform (106 g), n-butanol (35.0 g), respectively, after removal of the corresponding solvent The ethyl acetate soluble extract was fractionated by silica gel column chromatography eluted with chloroform and methanol gradients (100:0, 40:1: 30:1; 20:1; 10:1: 4:1; 2:1) to afford fractions (F1 to F7) Fraction F1 was subjected to silica gel column chromatography eluted with n-hexane/acetone (15:1) to afford MA6 (128 mg) Fraction F3 was subjected to silica gel column chromatography eluted with n-hexane/acetone (7:1) to afford MA3 (28 mg) and MA5 (31 mg) Fraction F5 was subjected to silica gel column chromatography eluted with chloroform: methanol (10:1) to afford MA4 (51 mg) The n-butanol soluble extract was fractionated by silica gel column chromatography eluted with chloroform and methanol gradients (30:1; 20:1; 10:1: 4:1; 2:1) to afford fractions Fraction was subjected to the silica gel column chromatography eluted with chloroform: methanol (15:1) to afford MA1 (12 mg) Fraction was subjected to the silica gel column chromatography eluted with chloroform: methanol (10:1) to afford MA2 (21.5 mg) Fraction was subjected to the silica gel column chromatography eluted with chloroform: methanol (10:1) to afford MA7 (41 mg) 10 2.6 Biological activity test Test anti-inflammatory activity and plant anti-fungal activity Evaluate the antifungal activity of compounds isolated with C acutatum, C fragariae, C gloeosporioides, F oxysporum, B cinerea P obscurans CHAPTER 3: RESULTS AND DISCUSSION 3.1 Fruits of Anphanamixis polystachya Table 3.1: Isolated compounds from fruits of Anphanamixis polystachya No Symbol Name of the compound Mass (mg) AP-1 AP-2 AP-3 AP-4 AP-5 AP-6 Dysobinin Chisocheton compound E chisocheton compound G 6α - acetoxyepoxyazadiradione VI β-sitosterol -Sitosterol-3-O--Dglucopyranoside 41 31 21 43 153 13 3.2 Fruits of Khaya senegalensis Table 3.2: Isolated compounds from fruits of Khaya senegalensis No Symbol Name of the compound Mass (mg) KS1 KS2 KS3 KS4 KS5 KS6 Seneganolide Khayanone Khayanolide B 6-Acetoxy-methyl angolensate (-)-Epicatechin Quercitrin 34 32 22 10 20 3.3 Fruits of Melia azedarach 3.3.1 Isolated compounds The process of isolating the substances from the fruits of Melia azedarach was presented in detail in the experimental section In the course of our research we have focused on studying the chemical composition of the methanol extract from leaves Annona reticulata by combining the methods of extraction, thin layer 11 chromatography, silica gel column chromatography, high performance liquid chromatography (HPLC) The results of the study are shown in Table 3.15 Table 3.15: Isolated compounds from fruits of Melia azedarach No Symbol Name of the compound Mass (mg) MA1 MA2 MA3 MA4 MA5 MA6 MA7 MA8 New Apigenin Quercetin 3-O-[-Lrhamnopyranosyl-(1→6)]--Dglucopyranoside Scopoletin Acid vanillic Taraxerol β-sitosterol -sitosterol-3-O--Dglucopyranoside 14 12 21,5 28 31 25 128 41 3.1.2 Structural elucidation of new compound MA1 Compound MA1 was isolated as optically active colorless syrup and the HRESIMS analytical data of revealed the molecular formula as C37H44O9 (m/z 655.2879, [M+Na]+) The UV absorption maxima at 205, 218, 244, and 273 nm indicated the presence of a conjugated benzene chromophore [99] The 1H-NMR spectrum of MA1 (Table 3.2) displayed the characteristic resonances for four methyl singlets [H 1.00 (6H, CH3-20, -22), 1.18 (3H, CH3-18), and 1.25 (3H, CH3-21)], one oxymethylene group [H 3.13 (m) and 3.45 (d, J = 7.5 Hz)], and one set of signals for furan moiety [H 6.16 (br s), 7.13 (br s), and 7.28 (br s)], respectively, which indicated the basic skeleton of MA1 was similar to that of trichilinins [48] In addition, there were also proton signals representative for two acetyl singlets [H 1.90 (3H) and 1.91 (3H)] and one benzoyl fragment [H 7.43 (2H, t, 7.5), 7.56 (1H, t, 7.5), and 8.08 (2H, d, 7.5)] Comparison of the above spectral data with those of trichilinin E [48], the observed difference in was the presence of one more acetyl group The substitution position of acetyl and benzoyl groups were determined by the assistance of comprehensive 2D NMR spectroscopic examinations of In the HMBC spectrum, 2J, 3J-HMBC correlations from H-3 to C-1, C-27; from H-6 to C-7; from H-7 to C-1'; from H12 to C-29; from H-15 to C-8, C-17; from H-17 to C-23, C-24, C-26; from CH3- 12 18 to C-3, C-4, C-19; from CH3-20 to C-1, C-5, C-9; from CH3-21 to C-14; from CH3-22 to C-12, C-14, C-17; from H-7' to C-1', respectively, were observed and established its 2D planar structure as shown (Figure 1) The other successive 2D experiments constructed the same stereochemical configurations of and completed the assignments of all the proton and carbon signals Conclusively, the chemical structure of was established as 3α,12α-diacetoxy-7α-benzoyloxy-1αhydroxytrichilinin (Figure 1) and named trivially as trichilinin F followed the previous convention Table 3.2: 1H and 13C-NMR data of MA1 STT δH (J =Hz) δC STT δH (J =Hz) δC 3.56 (br s) 71.8 20 1.00 (s) 15.8 1.53 (m) 2.27 (m) 24.3 21 1.25 (s) 27.1 5.08 (br s) 72.8 22 1.00 (s) 15.4 42.3 23 124.6 2.55 (d 12.5) 40.3 24 7.13 (br s) 140.2 4.27 (dd 12.5 3.0) 73.6 25 7.28 (br s) 141.9 5.85 (d 3.0) 74.2 26 6.16 (br s) 111.8 51.7 27 169.0 3.15 (dd 13.0 7.5) 36.2 28 1.91 (s) 20.8 10 44.1 29 171.0 11 2.04 (m) 2.36 (m) 30.0 30 1.90 (s) 21.3 12 5.08 (m) 77.8 1’ 165.0 13 40.2 2’ 130.6 14 155.7 3’ 8.08 (d 7.5) 129.5 15 5.70 (br s) 122.7 4’ 7.43 (t 7.5) 128.3 16 2.32 (m) 36.6 5’ 7.56 (t 7.5) 132.9 17 2.97 (dd 10.8 7.5) 50.4 6’ 7.43 (t 7.5) 128.3 18 1.18 (s) 18.8 7’ 8.08 (d 7.5) 129.5 19 3.13 (m) 3.45 (d 77.9 7.5) 13 (MA-1) A3α,12α-diacetoxy-7α-benzoyloxy-1α-hydroxytrichilinin Figure 3.16 The ESI-MS spectra of MA1 14 Figure 3.37 The HR-ESI-MS spectra of MA1 15 Figure 3.18 The 1H-NMR spectra of MA1 Figure 3.19 The 1H-NMR spectra of MA1 Figure 3.20 The 1H-NMR spectra of MA1 16 Figure 3.21 The 13C-NMR spectra of MA1 17 Figure 3.22 The 13C-NMR spectra of MA1 Figure 3.25 The DEPT spectra of MA1 18 Figure 3.27 The HMBC spectra of MA1 Figure 3.28 The HSQC spectra of MA1 19 Figure 3.29 The COSY spectra of MA1 3.3 Antimicrobial and antifungal activity of compounds The food-poisoned technique-used to quantify the antibiotic activity of compounds against Fusarium oxysporum is determined by mixing the substance into the molten PDA environment according to the test concentration (200 ppm and 500 ppm) Petri dishes after transplanting are incubated at 25 ° C after and days and measuring the diameter of the fungus The antifungal effect is calculated according to the formula: CV (%) =100 × (Dc-Dt)/(Dc-4) Where: Dc: fungus diameter on a petri-controlled plate; Dt: fungus diameter on petri dish with mixing substance and 4: diameter of PDA at center of disc 20 The chemical compounds isolated from the fruits of Anphanamixis polystachya O 23 O 22 21 12 12 17 11 16 14 15 10 10 O 13 16 OAc O OAc OH 20 17 11 13 O 23 22 21 20 14 15 OAc OAc (AP-1) Dysobinin (AP-2) Chisocheton compound G O O 23 22 21 21 12 10 O 24 13 16 14 10 15 O OAc OAc 25 26 O O 16 14 20 17 11 19 13 18 12 20 17 11 O 23 22 15 OAc OAc (AP-3) Chisocheton compound E (AP-4) 6α -Acetoxyepoxyazadiradione VI 29 28 29 28 21 18 19 24 23 13 17 11 14 10 HO (AP-5) β-Sitosterol 27 22 20 12 21 12 25 HOH2C O 4' HO HO 5' 3' 2' O 23 17 13 16 14 15 10 6' 27 24 18 11 26 16 15 19 22 20 1' OH (AP-6) -Sitosterol-3-O--D-glucopyranoside 25 26 21 The chemical compounds isolated from the fruits of Khaya senegalensis (KS-1) Seneganolide (KS-3) Khayanolide B (KS-5) (-)-Epicatechin (KS-2) Khayanone (KS-4) 6-Acetoxy-methyl angolensate (KS-6) Quercitrin 22 The chemical compounds isolated from the fruits of Melia azedarach (MA-1) 3α,12α-diacetoxy-7α-benzoyloxy-1α-hydroxytrichilinin (MA-2) Apigenin (MA-3) Quercetin 3-O-[-L-rhamnopyranosyl(1→6)]--D-glucopyranoside) (MA-4) Scopoletin (MA-6) Vanillin (MA-5) Taraxerol (MA-7) β-Sitosterol (MA-8) -Sitosterol-3-O--D-glucopyranoside 23 CONCLUSIONS Study on chemical constituents and biological activity of Anphanamixis polystachya fruits, Khaya senegalensis fruits and Melia azedarach fruits in Vietnam gains significant achievements which is as follows: From the extract of Anphanamixis polystachya fruits there have isolated and identified 06 compounds including: - 04 known limonoid compounds: dysobinin, chisocheton compound G, chisocheton compound E and 6α - acetoxyepoxyazadiradione VI; - 02 known sterol compounds: β-sitosterol, -sitosterol-3-O--Dglucopyranoside From the extract of Khaya senegalensis fruits have isolated and identified 06 compounds including: - 04 known limonoid compounds: seneganolide, khayanone, khayanolide B, 6acetoxy-methyl angolensate; - 02 known flavonoid compounds: (-)-epicatechin and quercitrin From the extract of Melia azedarach fruits have isolated and identified 06 compounds including: - 01 new limonoid compound: 3α,12α-diacetoxy-7α-benzoyloxy-1αhydroxytrichilinin (trichilinin F) - 02 known flavonoid compounds: apigenin and quercetin 3-O-[-Lrhamnopyranosyl-(1→6)]--D-glucopyranoside) - 01 known triterpenoid compound: taraxerol; - 02 phenolic compounds: scopoletin and acid vanillic; - 02 sterol compounds: β-sitosterol, -sitosterol-3-O--D-glucopyranoside Evaluation of antifungal activity of isolated compounds AP2, AP3, KS2, KS3, KS4 against Fusarium oxysporum The results showed that KS3 has strong antifungal activity with inhibitory effect of over 80% at 500ppm concentration and no decline after days of culture 24 PUBLISHED WORKS Vu Thi Hien, Tran Thi Ngoc Han, Pham Thi Hang, Tran Dinh Thang (2013), The tertranortriterpenoid compounds from the fruits of Anphanamixis polystachya (Wall.) Parker) (Meliaceae) in Vu Quang – Ha Tinh, Journal of Chemistry, T.51 (6ABC), 68-71 Vu Thi Hien, Nguyen Thi Thanh Phuong, Tran Dinh Thang (2014), The limonoid compounds from the fruits of Anphanamixis polystachya (Wall.) Parker) (Meliaceae), Journal of Science and Technology, T.52 (5A), 49-54 Vu Thi Hien, Vu Dinh Hoang (2016), Chemical constituents of fruits of Khaya senegalensis A Juss growing in Vietnam, Vietnam Journal of Chemistry, International Edition, 54(6) 781-785 Vu Thi Hien, Nguyen Ngoc Tuan, Hoang Van Luu, Vu Dinh Hoang (2018), Isolation and structure determination of compounds from Melia azedarach fruits in Vietnam, Journal of Science and Technology (Technical Universities) (Accepted) Vu Dinh Hoang, Vu Thi Hien, Nguyen Ngoc Tuan, Ping-Chung Kuo, Tian-Shung Wu, Tran Dinh Thang (2018), Chemical constituents of fruits of Melia azedarach growing in Vietnam, Nat Prod Res (submitted)  ... The tertranortriterpenoid compounds from the fruits of Anphanamixis polystachya (Wall.) Parker) (Meliaceae) in Vu Quang – Ha Tinh, Journal of Chemistry, T.51 (6ABC), 68-71 Vu Thi Hien, Nguyen... Thang (2014), The limonoid compounds from the fruits of Anphanamixis polystachya (Wall.) Parker) (Meliaceae), Journal of Science and Technology, T.52 (5A), 49-54 Vu Thi Hien, Vu Dinh Hoang (2016),