A sesquiterpenoid compound, and an extraction method and application thereof

Abstract

The application discloses a kind of sesquiterpenes compound, belong to medical technology field, it is from eaglewood knot heartwood ethanol extract PXS264 Dichloromethane extraction active part PXS272 Separation, identification five kinds of sesquiterpenes compound PGE90, PGE93a, PGE81, PGE82 and PGE83.This kind of compound has anti-tumor and anti-inflammatory activity, can be used to prepare the drug for preventing or treating tumor, inflammation related disease.The application first separates and identified new compound PGE90, PGE93a and PGE81, and first clarifies the anti-tumor and anti-inflammatory activity of the five sesquiterpenes compounds.By the method of the application, the above chemical components can be obtained simply and quickly from the soil eaglewood knot heartwood and its anticancer dichloromethane active part PXS272.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a sesquiterpene compound, its extraction method, and its application. Background Technology

[0002] Nitric oxide (NO) is an important multifunctional signaling molecule in the body, produced by excessive production of iNOS, a pro-inflammatory enzyme. Under physiological conditions, adequate NO participates in normal physiological processes such as vasodilation, neurotransmission, and immune defense. However, excessive NO production can trigger or exacerbate various inflammatory diseases, such as rheumatoid arthritis, asthma, sepsis, neurodegenerative diseases, and cancer [JN Shaema, A. AI-Omran, SS Parvathy. Role of nitric oxide in inflammatory diseases. Inflammopharmacology, 2007, 15 (6):252-259.]. In the treatment of inflammatory diseases, inhibiting NO production has become an important research direction. Clinical studies have confirmed that chronic inflammation is closely related to the occurrence and development of various malignant tumors, and approximately 15% to 20% of cancer deaths are directly or indirectly related to underlying inflammatory states. Therefore, inhibiting excessive NO production is one of the important strategies for developing anti-inflammatory and anti-inflammatory tumor drugs.

[0003] Agarwood, also known as white agarwood [ Aquilaria sinensis [Lour.) Spreng.] is a plant belonging to the genus Aquilaria in the family Thymelaeaceae. Its resinous heartwood is the traditional Chinese medicine agarwood. Agarwood has the effects of promoting qi circulation and relieving pain, warming the middle jiao and stopping vomiting, and calming qi and relieving asthma. It is used to treat chest and abdominal distension and pain, aversion to cold, vomiting and hiccups, and kidney deficiency with shortness of breath [National Pharmacopoeia Commission. Pharmacopoeia of the People's Republic of China (Part I). Beijing: China Medical Science and Technology Press. 2020, 192-193]. The "Dictionary of Anti-cancer Traditional Chinese Medicines" lists that agarwood, when combined with other traditional Chinese medicines, can treat esophageal cancer, liver cancer, complete obstruction of the pylorus, gastric cancer, malignant lymphoma and other cancers [Liu Chun'an, Peng Ming. Dictionary of Anti-cancer Traditional Chinese Medicines. Wuhan: Hubei Science and Technology Press, 1994.].

[0004] No sesquiterpene derivatives have been found in the existing technology (7) S 9 S 10 SThe reports on these three novel sesquiterpenoid compounds—(7R,10S)-12,15-dihydroxyeucalyptol-4,11(13)-diene-3-one, and (4S,5R,7R,10S)-5,11-epoxy-4-hydroxyeucalyptol-15-aldehyde—have not included any studies on their anti-inflammatory and antitumor activities. Furthermore, although compounds 12,15-dioxo-α-ostrichene and ostrich-4,11(13)-diene-12,15-dialdehyde are known natural products, their anti-inflammatory and antitumor activities, as well as any other medicinal value, have not been publicly reported, and there is a gap in research on their isolation, preparation methods, and pharmaceutical applications. Summary of the Invention

[0005] This invention provides a sesquiterpene compound, wherein the sesquiterpene compound is selected from compounds represented by formulas A, B, C, D, and E: .

[0006] A method for extracting sesquiterpenoid compounds from the heartwood of Aquilaria sinensis includes the following steps: A method for extracting sesquiterpenoid compounds from the heartwood of Aquilaria sinensis includes the following steps: (1) Take the heartwood of Aquilaria sinensis and crush it into powder. Add ethanol and extract it by ultrasonic extraction 6-8 times. The liquid is recovered under reduced pressure and concentrated to obtain the ethanol extract for later use. (2) Dissolve the ethanol extract in water and extract it 3-5 times in sequence with equal volumes of petroleum ether, dichloromethane, ethyl acetate and n-butanol to obtain the petroleum ether fraction, dichloromethane fraction, ethyl acetate fraction, n-butanol fraction and water fraction respectively. (3) The dichloromethane fraction was separated and extracted stepwise to obtain sesquiterpenoid compounds with different structures.

[0007] Furthermore, the volume fraction of ethanol in step (1) is 90%; the ultrasonic extraction is specifically performed under a water bath at 60°C.

[0008] Furthermore, the stepwise separation and extraction described in step (3) is to obtain the five sesquiterpene compounds with different structures as described in claim 1. Specifically, the compound corresponding to formula A is (7S,9S,10S)-9,11-dihydroxyeucalyptol-4-en-3-one (PGE90); the compound corresponding to formula B is (7R,10S)-12,15-dihydroxyeucalyptol-4,11(13)-dien-3-one (PGE93a); the compound corresponding to formula C is (4S,5R,7R,10S)-5,11-epoxy-4-hydroxyeucalyptol-15-aldehyde (PGE81); the compound corresponding to formula D is 12,15-dioxo-α-ostrichene (PGE82); and the compound corresponding to formula E is ostrich-4,11(13)-dien-12,15-dialdehyde (PGE83).

[0009] Furthermore, the specific operation of the step-by-step separation and extraction described in step (3) is as follows: 1) The dichloromethane fraction was separated by silica gel column chromatography, yielding 12 fractions, labeled as Fr.B1-Fr.B12; 2) The Fr. B2 fraction was subjected to C18 reversed-phase silica gel column chromatography and eluted with methanol-water gradient to obtain 9 fractions, labeled as Fr.B2-1 ~ Fr.B2-9; 3) Fr. B2-3 was separated into two fractions using a Sephadex LH-20 gel chromatography column, labeled as Fr. B2-3-1 and Fr. B2-3-2 respectively; 4) Fr. B2-3-2 was divided by normal phase silica gel column chromatography and eluted with a gradient of petroleum ether-ethyl acetate system to obtain compounds PGE81, PGE82 and PGE83; 5) Fr. B10 was subjected to RP-18 reversed-phase silica gel column chromatography and eluted with methanol-water gradient to obtain 14 fractions, labeled as Fr. B10-1 ~ Fr. B10-14; 6) Fr. B10-2 was recrystallized from methanol to obtain two parts: Fr. B10-2-1 and Fr. B10-2-2. 7) Fr. B10-2-2 was further separated by elution with a concentration gradient of petroleum ether-acetone system using a normal-phase silica gel column to obtain a total of 12 fractions, Fr. B10-2-2-1 to Fr. B10-2-2-12; 8) Fr. B10-2-2-4 was separated into four fractions, Fr. B10-2-2-4-1 ~ Fr. B10-2-2-4-4, by Sephadex LH-20 gel chromatography; 9) Fr. B10-2-2-4-1 was separated by normal phase silica gel column chromatography and eluted with a dichloromethane-acetone system to obtain 6 fractions Fr. B10-2-2-4-1-1 ~ Fr. B10-2-2-4-6; 10) Fr. B10-2-2-4-1-4 was separated by semi-preparative HPLC to obtain two fractions: compound PGE90 and Fr. B10-2-2-4-1-4-2; 11) Fr. B10-2-2-4-1-4-2 was further separated by reverse-phase semi-preparative HPLC to obtain compound PGE93a.

[0010] Furthermore, in step 1), the chromatographic separation is performed using a petroleum ether-ethyl acetate system with a gradient of 20:1-0:1; in step 2), the methanol-water system has a gradient of 50%-100%; in step 4), the petroleum ether-ethyl acetate system has a gradient of 20:1; in step 5), the methanol-water system has a gradient of 30%-100%; in step 7), the normal-phase silica gel column is 200-300 mesh, and the petroleum ether-acetone system has gradients of 9:1, 3:1, 2:1, 1:1, and 0:1; in step 9), the dichloromethane-acetone system has gradients of 20:1, 15:1, 10:1, 5:1, and 3:1.

[0011] Furthermore, in step 10), the semi-preparative HPLC column size is 4.6 × 250 mm, the eluent used is n-hexane-isopropanol with a ratio of 90:10, and the flow rate is controlled at 1 mL / min; in step 11), the semi-preparative HPLC column size is 4.6 × 250 mm, the eluent used is acetonitrile-water with a ratio of 20:70, and the flow rate is controlled at 1 mL / min.

[0012] The application of a sesquiterpene compound, said sesquiterpene compound being used in drugs for the prevention and treatment of leukemia, lung cancer, breast cancer, colon cancer, and anti-inflammatory purposes.

[0013] Furthermore, the sesquiterpene compound is at least one of the following: (7S,9S,10S)-9,11-dihydroxyeucalyptol-4-en-3-one corresponding to Formula A, (7R,10S)-12,15-dihydroxyeucalyptol-4,11(13)-dien-3-one corresponding to Formula B, (4S,5R,7R,10S)-5,11-epoxy-4-hydroxyeucalyptol-15-aldehyde corresponding to Formula C, 12,15-dioxo-α-ostrichene corresponding to Formula D, and ostrichene-4,11(13)-dien-12,15-dialdehyde corresponding to Formula E.

[0014] This invention explores in detail the active components and novel compound structures in the heartwood of *Aquilaria sinensis*. For the first time, it locates and elucidates the effective component with significant anticancer activity from the heartwood of *Aquilaria sinensis*: the dichloromethane extract. From this extract, three novel sesquiterpenoid compounds were isolated and identified: (7S,9S,10S)-9,11-dihydroxyeucalyptol-4-en-3-one (PGE90), (7R,10S)-12,15-dihydroxyeucalyptol-4,11(13)-dien-3-one (PGE93a), and (4S,5R,7R,10S)-5,11-epoxy-4-hydroxyeucalyptol-15-aldehyde (PGE81). The two known compounds with the best activity are 12,15-dioxo-α-ostrichene (PGE82) and ostrichene-4,11(13)-dien-12,15-dialdehyde (PGE83).

[0015] This invention confirms that these sesquiterpenes and the dichloromethane extracts of Aquilaria sinensis (Fr. B2, Fr. B3, Fr. B4, Fr. B5, Fr. B6, Fr. B7, Fr. B8, Fr. B9, Fr. B10, Fr. B11, or Fr. B12 exhibit broad-spectrum and significant antitumor activity, showing marked inhibitory activity against leukemia HL-60 cells, lung cancer A549 cells, lung cancer A549 / Taxol cells, lung cancer NCI-H520 cells, breast cancer MDA-MB-232 cells, and colon cancer SW480 cells.

[0016] The active ingredient extracted in this invention exhibits breakthrough inhibitory activity against paclitaxel-resistant lung cancer cells. In particular, Fr. B9 (IC) 50 =0.38 m The inhibitory activity of (g / mL) on lung cancer A549 / Taxol-resistant cells was significantly better than that of the positive control paclitaxel (IC50 g / mL). 50 =0.84 m (g / mL). The components extracted in this invention exhibit significantly better inhibitory effects on the activity of various sensitive tumor cells than the clinical drug cisplatin.

[0017] Fr. B8 (IC) 50 =1.86 m g / mL) and Fr. B9 (IC) 50 =0.41 m The inhibitory activity of (g / mL) on lung cancer A549 cells was significantly higher than that of the positive control cisplatin (IC50 g / mL). 50 =5.55 m g / mL). Fr. B2 (IC) 50 =1.97 m g / mL), Fr. B3 (IC 50 =3.21 mg / mL), Fr. B9 (IC 50 =1.67 m g / mL) and Fr. B11 (IC 50 =2.84 m The inhibitory activity of (g / mL) on breast cancer MDA-MB-232 cells was higher than that of the positive control cisplatin (IC50 / mL). 50 =5.91 m g / mL). Fr. B2 (IC) 50 =0.57 m g / mL), Fr. B9 (IC 50 =0.86 m The inhibitory activity of (g / mL) on colon cancer SW480 cells was significantly better than that of the positive control cisplatin (IC50 / mL). 50 =2.03 m g / mL). Fr. B2 (IC) 50 =2.77 m g / mL), Fr. B8 (IC 50 =0.31 m g / mL), Fr. B9 (IC 50 =0.30 m g / mL) and Fr. B11 (IC 50 =4.32 m The inhibitory activity of (g / mL) on NCI-H520 lung cancer cells was significantly higher than that of the positive control cisplatin (IC50 g / mL). 50 =5.39 m g / mL).

[0018] The first experiments have revealed new applications of the known compounds 12,15-dioxo-α-ostrichene (PGE82) and ostrich-4,11(13)-diene-12,15-dialdehyde (PGE83) in antitumor and anti-inflammatory applications. 12,15-dioxo-α-ostrichene (PGE82) exhibits broad-spectrum cytotoxic activity.

[0019] The new compound (4S,5R,7R,10S)-5,11-epoxy-4-hydroxyeucalyptane-15-aldehyde (PGE81, IC) 50 =25.65 m M), 12,15-dioxo-α-sericeene (PGE82) (IC 50 =0.19 m M) and Cnidium-4,11(13)-diene-12,15-dialdehyde (PGE83, IC) 50 =10.19 m The anti-inflammatory activity of M) was superior to that of the positive control L-NMMA (IC). 50 =39.71 m M).

[0020] The present invention has the following advantages over the prior art: 1. This invention is the first to discover new compounds and active parts: for the first time, a dichloromethane extract with significant anticancer activity was located from the heartwood of Aquilaria sinensis, and three novel eucalyptane-type sesquiterpenoid compounds were isolated from it. At the same time, the anti-inflammatory and antitumor uses of two known compounds were discovered for the first time.

[0021] 2. The extract has broad-spectrum and highly effective anti-tumor activity: The extract and compounds of this invention have significant inhibitory effects on various tumor cells such as leukemia, lung cancer, breast cancer, and colon cancer. The inhibitory effect of multiple active sites is superior to that of cisplatin, a commonly used chemotherapy drug in clinical practice.

[0022] 3. Breakthrough effect against drug-resistant tumor cells: The Fr. B9 site of this invention exhibits superior inhibitory activity against paclitaxel-resistant lung cancer cells A549 / Taxol compared to the positive control paclitaxel, which can solve the problem of drug resistance in clinical chemotherapy.

[0023] 4. Excellent anti-inflammatory activity: The multiple sesquiterpenoid compounds in this invention can effectively inhibit LPS-induced excessive NO production, and their anti-inflammatory activity is superior to that of the positive control drug L-NMMA, which can be used to treat inflammation-related diseases.

[0024] 5. Efficient separation and preparation method: This invention establishes a process for efficiently separating the above-mentioned active components and target compounds from the heartwood of Aquilaria sinensis. By combining multiple chromatographic separation techniques, high-purity target products can be obtained stably and rapidly, providing a feasible technical foundation for subsequent drug development and industrialization. Attached Figure Description

[0025] Figure 1 This is a schematic diagram of the chemical structures of PGE90, PGE93a, PGE81, PGE82 and PGE83 extracted according to the present invention; Figure 2 Two-dimensional nuclear magnetic resonance correlation diagrams for the key compounds PGE90, PGE93a, and PGE81 extracted in this invention; Figure 3 The crystal diffraction structure of compound PGE90 extracted in this invention; Figure 4 This invention extracts calculated and experimental electron circular dichroism (ECD) chromatograms of compounds PGE90, PGE93a, and PGE81. Detailed Implementation

[0026] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions in the embodiments of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of the embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0027] In the embodiments, it should be noted that any processes not specifically described below are those that can be implemented or understood by those skilled in the art by referring to existing technology. Reagents or instruments whose manufacturers are not specified are considered to be conventional products that can be purchased commercially.

[0028] Example 1 Preparation of dichloromethane fraction: 1.59 kg of agarwood heartwood was collected, pulverized into powder, and then extracted with 90% ethanol. The mixture was ultrasonically extracted in a 60 °C water bath for 1 hour, repeated 8 times. The extract was recovered under reduced pressure and concentrated to obtain 216.7 g of ethanol extract (labeled PXS264). The crude extract was dissolved in an appropriate amount of water and extracted 3-5 times sequentially with equal volumes of petroleum ether, dichloromethane, ethyl acetate, and n-butanol to obtain the petroleum ether fraction, dichloromethane fraction (labeled PXS272), ethyl acetate fraction, n-butanol fraction, and water fraction, respectively.

[0029] Example 2: PXS272 was prepared in fractions using silica gel column chromatography, and the chemical components of the sesquiterpene derivatives were separated: PXS272 was separated by silica gel column chromatography in petroleum ether-ethyl acetate (20:1-0:1) to obtain 12 fractions, including Fr.B1-Fr.B12.

[0030] The Fr. B2 fraction was subjected to C18 reversed-phase silica gel column chromatography and eluted with a gradient of methanol-water (50%-100%) to obtain 9 fractions, from Fr. B2-1 to Fr. B2-9.

[0031] Fr. B2-3 was separated into two fractions, Fr. B2-3-1 and Fr. B2-3-2, using a Sephadex LH-20 gel chromatography column (MeOH).

[0032] Fr. B2-3-2 was divided by normal phase silica gel column chromatography (H silica gel) and eluted with a petroleum ether-ethyl acetate system (20:1) to obtain compounds PGE81, PGE82 and PGE83.

[0033] Fr. B10 was subjected to RP-18 reversed-phase silica gel column chromatography with gradient elution using methanol-water (30%-100%) to obtain 14 fractions from Fr. B10-1 to Fr. B10-14.

[0034] Fr. B10-2 was recrystallized from methanol to obtain two parts: Fr. B10-2-1 and Fr. B10-2-2.

[0035] Fr. B10-2-2 was separated by elution with a normal-phase silica gel column (200-300 mesh) and a petroleum ether-acetone system (9:1, 3:1, 2:1, 1:1, 0:1) to obtain a total of 12 fractions, Fr. B10-2-2-1 to Fr. B10-2-2-12.

[0036] Fr. B10-2-2-4 was separated into four fractions, Fr. B10-2-2-4-1 ~ Fr. B10-2-2-4-4, by Sephadex LH-20 gel chromatography (MeOH).

[0037] Fr. B10-2-2-4-1 was separated by normal phase silica gel column chromatography (H silica gel), and after elution with dichloromethane-acetone systems (20:1, 15:1, 10:1, 5:1, 3:1), six fractions Fr. B10-2-2-4-1-1 ~ Fr. B10-2-2-4-5 were obtained.

[0038] Fr. B10-2-2-4-1-4 was separated into two fractions, PGE90 and Fr. B10-2-2-4-1-4-2, by semi-preparative HPLC (Agilent 1200 HPLC system, CHIRALPAK AD-H column, φ 4.6×250 mm, n-hexane-isopropanol, 90:10, flow rate 1 mL / min).

[0039] Fr. B10-2-2-4-1-4-2 was further separated by reversed-phase semi-preparative HPLC (Agilent 1200 liquid chromatograph, Chiral CD-PH column, φ4.6×250 mm, acetonitrile-water, 20:70, flow rate 1 mL / min) to obtain compound PGE93a.

[0040] Example 3 Spectroscopic data and structural analysis of compounds (7S,9S,10S)-9,11-dihydroxyeucalyptol-4-en-3-one (PGE90), (7R,10S)-12,15-dihydroxyeucalyptol-4,11(13)-dien-3-one (PGE93a), (4S,5R,7R,10S)-5,11-epoxy-4-hydroxyeucalyptol-15-aldehyde (PGE81), 12,15-dioxo-α-ostrichene (PGE82), and ostrichene-4,11(13)-dien-12,15-dialdehyde (PGE83): Compound PGE90 is a colorless, transparent, needle-like crystal, CH2-Cl2-MeOH (1:1). Based on the high-resolution mass spectrometry data of compound PGE90, i.e., HR-ESI-MS m / z 252.172 1 [M + H],... + (The calculated value is C) 31 H 44 NaO8, 252.172 0), combined 1 H and 13 Based on the 10⁻¹⁴ C NMR data (see Table 1), the molecular formula of PGE90 is deduced to be C⁻¹. 31 H 44 O8 has 4 degrees of unsaturation.

[0041] 1 The 1H NMR spectrum showed four singlet signals for methyl groups: δ H 1.27 (3H, s), 1.26 (3H, s), 1.80 (3H, s) and 1.16 (3H, s). 13 C10 NMR data analysis indicated the presence of an α,β-unsaturated ketone unit (δ¹⁺). C 198.9, 160.0, and 130.6), two quaternary carbons, one of which is an oxygen-containing quaternary carbon (δ). C 72.1 and 41.4), two methines, one of which is an oxygen-containing methine (δ C 78.4 and 45.3), four methylene groups (δ C 33.5, 33.4, 31.3 and 28.1), and four methyl groups (δ). C 27.6, 26.9, 15.7 and 11.4).

[0042] COSY correlation spectrum of compound PGE90 (see appendix) Figure 2 This revealed the existence of two fragments: H2-1 / H2-2 and H2-6 / H-7 / H2-8 / H-9. The key HMBC correlation spectrum (see appendix) Figure 2In the ROESY correlation spectrum, the correlation signals from H3-15 to C-3, C-4, and C-5 indicate that the methyl group (C-15) is attached to C-4 of the α,β-unsaturated ketone moiety; the correlation signals from H3-14 to C-1, C-5, C-9, and C-10, from H2-1 to C-3, from H2-6 to C-4 and C-10, and from H3-12 and H3-13 to C-7 and C-11 construct a planar structure: 9,11-dihydroxyeucalyptol-4-en-3-one. The relative configuration of compound PGE90 was determined by ROESY correlation spectroscopy (see Appendix). Figure 2 The correlation signals of H-1β / H3-14 indicate that the 10-methyl group should be β-oriented. The correlation signals of H-1α / H-9 and H-9 / H-7 indicate that H-9 and H-7 should be α-oriented, while 9-OH should be β-oriented. The ECD spectra of the (7R,9R,10R)- and (7S,9S,10S)- isomers of compound PGE90 were calculated. The experimentally measured ECD spectra matched the calculated spectra of the (7S,9S,10S)- isomer (see Appendix). Figure 4 Therefore, the absolute configuration of compound 1 was determined to be (7S,9S,10S)-9,11-dihydroxyeucalyptol-4-en-3-one. This configuration was further confirmed by Cu-Kα radiation X-ray single-crystal diffraction with a Flack parameter of 0.02(13) (see Appendix). Figure 3 ).

[0043] Spectral data of (7S,9S,10S)-9,11-dihydroxyeucalyptol-4-en-3-one (PGE90): (7S,9S,10S)-9,11-dihydroxyeucalyptol-4-en-3-one (PGE90), colorless transparent needle-like crystals, CH2-Cl2-MeOH (1:1); α ]25 D+9 (c = 0.2, MeOH); UV (MeOH) λmax (log ε) 249 (3.20), 202(2.97) nm; ECD (6.75 mM, MeOH) λmax (Δε) 319 (−0.15), 247 (+0.88), 205 (+0.67) nm; 1 H and 13 C10 NMR data, see Table 1; ESIMS (positive) m / z 275 [M + Na] + ;HREIMSm / z 252.172 1 [M] + (calcd for C 15 H 24 O3, m / z 252.172 0).

[0044] Table 1

[0045] a 1 H (600 MHz) and 13 C10 NMR (150 MHz), solvent CDCl3. b 1 H (800 MHz) and 13 C10 NMR (175 MHz), solvent CDCl3. c 1 H (500 MHz) and 13 C10 NMR (126 MHz), solvent CDCl3.

[0046] Compound PGE93a is a pale yellow oil. It was analyzed by high-resolution mass spectrometry (HRESIMS). m / z 273.146 2 [M +Na]⁺, calculated value is C 15 H 22 O3Na, 275.146 1) Determine its molecular formula as C 15 H 22 O3Na (unsaturation degree 5). Comparative analysis of the NMR data of compound PGE93a and compound PGE90 revealed that they share the same eucalyptane-type sesquiterpene skeleton. Key structural differences are as follows: 1) C-9 position: the chemical shift at C-9 ( d C 41.8) is consistent with (+)-carissone [F. Peng, M. Dai, AR, Angeles, SJ, Danishefsky, Permuting diels-alder and robinsonannulation stereopatterns. Chemical Science, 2012, 3(10), 3076–3080], indicating that there is no hydroxyl substitution at this position (compare compound 1, d C 78.4); 2) C-4 substituents and C-7 side chains: three methyl single-peak signals (H3-12, H3-13, H3-15) in compound PGE90; d H The signals 1.27, 1.26, and 1.16 disappeared, and were replaced by three sets of methylene proton signals. d H[5.13 (1H, br s) and 4.99 (1H, br s); 4.37 (2H, br s); 4.18 (2H, m)], suggesting that C-12 and C-15 may be oxidized to hydroxymethyl, and that a double bond is formed between C-11 and C-13 through dehydrogenation.

[0047] Through COSY correlation spectrum (see appendix) Figure 2 Two fragments were revealed: H2-1 / H2-2 and H2-6 / H-7 / H2-8 / H2-9. In the key HMBC correlation spectrum, the correlation signals from H2-12 and H2-13 to C-7, C-11 and C-12 confirmed that a 3-hydroxypropyl-1-en-2-yl unit was attached to C-7. The correlation signals from H3-14 to C-1, C-5, C-9 and C-10, and from H2-15 to C-3, C-4 and C-5 indicated that C-14 and C-15 were located on C-10 and C-4, respectively. Thus, the planar structure of compound PGE93a was determined to be 12,15-dihydroxyeucalyptol-4,11(13)-dien-3-one.

[0048] In the ROESY spectrum of compound PGE93a, correlation signals between H-1β / H3-14 and H-9β / H3-14 were observed (see appendix). Figure 2 The correlation signals of H-1α / H-9α and H-9α / H-7 indicate that H-7 should be α-oriented. ECD calculations (see appendix) show that the 10-methyl group is β-oriented. Figure 4 The absolute configuration of compound 2 was determined. The experimental ECD spectrum matched well with the calculated spectrum of the (7R,10S)-isomer. Therefore, the chemical structure of compound PGE93a was identified as (7R,10S)-12,15-dihydroxyeucalyptol-4,11(13)-dien-3-one.

[0049] Spectral data of (7R,10S)-12,15-dihydroxyeucalyptol-4,11(13)-dien-3-one (PGE93a): (7R,10S)-12,15-dihydroxyeucalyptol-4,11(13)-dien-3-one (PGE93a), pale yellow oil, [ α ]25D+5 ( c = 0.2, MeOH); UV (MeOH) l max (log e ) 245 (3.37), 200 (3.09) nm; ECD (4.00mM, MeOH) l max (Δ e) 318 (−0.21), 241 (+1.31) nm; 1 H and 13 C10 NMR data are shown in Table 1; ESIMS (positive) m / z 273 [M + Na] + HRESIMS m / z 273.146 2 [M + Na] + (calcd forC 15 H 22 O3Na, m / z 273.146 1).

[0050] Compound PGE81 is a pale yellow oil. According to HRESIMS (… m / z 275.161 7 [M + Na]⁺, calculated value is C 15 H 24 O3Na, 275.161 7), combined with ¹H and ¹³C NMR data (Table 1), its molecular formula was determined to be C. 15 H 24 O3 (unsaturation degree 4). ¹H NMR spectrum shows three methyl singlet signals: δ H 1.42 (3H, s), 1.29 (3H, s), and 0.88 (3H, s), and an aldehyde proton signal: δ H 9.57 (¹H, d, J = 1.6 Hz). ¹³C NMR data analysis indicates the presence of an aldehyde group (δ¹⁸). C 201.3), four quaternary carbons (δ) C 88.0, 82.2, 75.2 and 39.5), hexamethylene (δ) C 36.8, 36.4, 32.2, 30.9, 24.4 and 18.6) and three methyl groups (δ C (30.0, 22.5, and 22.4). Comparison of its NMR data with those of compounds PGE90 and PGE93a suggests that this compound may also be a eucalyptane-type sesquiterpene.

[0051] COSY related spectra (see appendix) Figure 2 The study revealed two fragments: H2-1 / H2-2 / H2-3 and H2-6 / H-7 / H2-8 / H2-9. HMBC correlation spectra (see appendix) Figure 2From H3-12 and H3-13 to C-7 and C-11, from H3-14 to C-1, C-5, C-9 and C-10, from H-15 to C-3, from the 4-OH proton to C-5 and C-15, and from H-3α to C-5, the planar structure of 5,11-epoxy-4-hydroxyeucalyptane-15-aldehyde can be constructed. This structure is consistent with the octahydro-9-hydroxy-2,2,5a-trimethyl-2H-3,9a-methano-1-benzoxepin-9-carboxaldehyde reported in the literature [G. Buechi, H. Wueest, New synthesis of β-agarofuran and of dihydroagarofuran, The Journal of Organic Chemistry. 1979, 44(4), 546–549.].

[0052] Through ROESY correlation spectrum (see appendix) Figure 2 Further deduction of the relative configuration of compound PGE81. The correlation signals of H-9α / H3-14 and H3-14 / H-6α, and the correlation signal of H-9β / H3-13, indicate that the 10-methyl and C-5-C-6-C-7 bridges should be α-oriented, while the C-5-OC-11-C-7 bridge should be β-oriented. The correlation signal of H-6β / 4-OH indicates that 4-OH should be β-oriented, which is different from the known α-hydroxy aldehydes [G. Buechi, H. Wueest, New synthesis of β-agarofuran and ofdihydroagarofuran, The Journal of Organic Chemistry. 1979, 44(4), 546–549.]. Calculations were performed using ECD (see Appendix). Figure 4 The absolute configuration of compound PGE81 was determined. The experimental ECD spectrum matched the calculated spectrum of the (4S,5R,7R,10S)-isomer. Therefore, the chemical structure of compound PGE81 was identified as (4S,5R,7R,10S)-5,11-epoxy-4-hydroxyeucalyptane-15-aldehyde.

[0053] Spectroscopic data of compound (4S,5R,7R,10S)-5,11-epoxy-4-hydroxyeucalyptane-15-aldehyde (PGE81): Compound (4S,5R,7R,10S)-5,11-epoxy-4-hydroxyeucalyptane-15-aldehyde (PGE81), pale yellow oil, [ α ]25 D−48 ( c= 0.2, MeOH); UV (MeOH) l max (log e ) 267 (2.36), 213 (3.02), 204 (3.06); ECD ( c = 5. 40 mM, MeOH) l max (Δ e ) 311(−0.62), 251 (−0.02), 218 (+0.10); 1 Hand 13 C NMR data are shown in Table 1; ESIMS m / z 275 [M + Na] + HRESIMS m / z 275.161 7 [M + Na] + (calcd for C 15 H 22 O3Na, m / z 275.161 8).

[0054] Spectral data of compound 12,15-dioxo-α-sericeene (PGE82): Compound 12,15-dioxo-α-sericeene [(−)-(5 R 7 R 10 R )-12,15-dioxo- α -selinene, PGE82], colorless oil, C 15 H 20 O2; [ α ]20 D −7 ( c 0.2, MeOH) 1 H NMR (CDCl3, 500 MHz) d H 9.52 (1H, s, H-12), 9.41 (1H, s, H-15), 6.72 (1H, m, H-3), 6.27 (1H, br s, H-13a), 5.97 (1H, s, H-13b), 2.73 (1H, m, H-5), 2.61 (1H, m, H-7), 0.85 (3H, s, H3-14); 13 C NMR (CDCl3, 125 MHz) d C194.9 (C-12), 194.6 (C-15), 154.8 (C-11), 153.3 (C-3), 142.0 (C-4), 133.4 (C-13), 43.5 (C-5), 39.6 (C-9), 37.0 (C-7), 36.5 (C-1), 32.1 (C-10), 27.0 (C-6), 26.3 (C-8), 24.5 (C-2), 15.8 (C-14); ESIMS m / z 255 [M + Na] + Its NMR data is consistent with the literature [F. Bohlmann, C. Zdero, J. Cuatrecasas, RM King, H. Robinson, Neue sesquiterpene und norditerpene ausvertretern der gattung]. Libanothamnus The data are largely consistent with those in Phytochemistry 19 (1980) 1145–1148.

[0055] Spectral data of compound Selina-4,11(13)-diene-12,15-dia (PGE83): Selina-4,11(13)-diene-12,15-dia, PGE83, colorless oil, C 15 H 20 O2; [ α ]20 D +16 ( c 0.1, MeOH); 1 H NMR (CDCl3, 500 MHz) d H 10.15 (1H, s, H-15), 9.55 (1H, s, H-12), 6.33 (1H, br s, H-13a), 6.06 (1H, s, H-13b), 1.22 (3H, s, H3-14); 13 C NMR (CDCl3, 125 MHz) d C194.2 (C-12), 190.9 (C-15), 162.8 (C-5), 153.5 (C-11), 133.4 (C-13), 133.2 (C-4), 41.3 (C-9), 39.3 (C-1), 38.4 (C-7), 36.6 (C-10), 29.0 (C-6), 26.7 (C-8), 25.1 (C-14), 23.8 (C-3), 17.7 (C-2); EIMS m / z (rel. int.) 232 [M] + (35), 214 (32), 177 (60), 175 (37), 159 (49), 119 (58), 105 (58), 91 (100), 82 (75). Its NMR data and literature [Q. He, DB Hu, L. Zhang, MY Xia, H. Yan, XN Li, JFLuo, YS Wang, JH Yang, YH Wang, Neuroprotective compounds from theresinous heartwood of Aquilaria sinensis . Phytochemistry, 2021, 181, 112554. and S. Li, Y. Deng, D.-B. Hu, J.-F. Luo, P.-J. Zhao, J. Yang, Y.-H. Wang, Chemical constituents, biological activities, and quality evaluation of agarwood produced from the qi-nan germplasm of Aquilaria sinensis The data are largely consistent with those in Phytochemistry Letter, 2025, 65, 68–76.

[0056] Example 4:

[0057] Inhibitory effect of PXS272 on tumor cell growth: Cancer cell cytotoxicity was assessed using the MTS method [Yang J, Hu DB, Xia MY, Luo JF, Li XY, Wang YH. Bioassay-guided isolation of cytotoxic constituents from the flowers of Aquilaria sinensis. Natural Products and Bioprospecting, 2022, 12, 1-11], with cisplatin and paclitaxel as positive controls. The results of the cytotoxicity assay are shown in Table 2 below. The results showed that PXS271 exhibited inhibitory activity against various cancer cell lines, including leukemia HL-60, lung cancer A549, breast cancer MDA-MB-231, colon cancer SW480, and the paclitaxel-resistant lung cancer cell line A549 / Taxol. The half-maximal inhibitory concentration (IC50) of PXS272 was [not specified in the original text]. 50 = 1.27–10.20 m The concentration of g / mL was significantly higher than that of the positive control cisplatin (IC50 g / mL). 50 = 15.06–100 m (g / mL); This indicates that PXS272 has broad-spectrum inhibitory activity against the growth of different cancer cells and normal human lung epithelial cells.

[0058] Table 2

[0059] Example 5: PXS272 was prepared by silica gel column chromatography, and the inhibitory effects of Fr.B2, Fr.B3, Fr.B4, Fr.B5, Fr.B6, Fr.B7, Fr.B8, Fr.B9, Fr.B10, Fr.B11, and Fr.B12 on cancer cell growth were obtained.

[0060] Cancer cytotoxicity activity was tested using the MTS method [Yang J, Hu DB, Xia MY, Luo JF, Li XY, Wang YH. Bioassay-guided isolation of cytotoxic constituents from the flowers of Aquilaria sinensis. Natural Products and Bioprospecting, 2022, 12, 1-11], with cisplatin and paclitaxel as positive controls. The results of the cytotoxicity test are shown in Table 3 below. The results showed that the dichloromethane extract fractions (PXS272) Fr.B2, Fr.B3, Fr.B4, Fr.B5, Fr.B6, Fr.B7, Fr.B8, Fr.B9, Fr.B10, Fr.B11, and Fr.B12 all exhibited broad-spectrum cytotoxic activity. In particular, Fr. B9 (IC50) showed the highest cytotoxicity. 50 =0.38 m The inhibitory activity of (g / mL) on lung cancer A549 / Taxol-resistant cells was significantly better than that of the positive control paclitaxel (IC50 g / mL). 50 =0.84 m (g / mL). Multiple fractionated sites showed significantly superior activity against a variety of sensitive tumor cells compared to the clinical drug cisplatin. Fr. B8 (IC 50 =1.86 m g / mL) and Fr.B9 (IC) 50 =0.41 m The inhibitory activity of (g / mL) on lung cancer A549 cells was significantly higher than that of the positive control cisplatin (IC50 g / mL). 50 =5.55 m g / mL). Fr. B2 (IC) 50 =1.97 m g / mL), Fr. B3 (IC 50 =3.21 m g / mL), Fr. B9 (IC 50 =1.67 m g / mL) and Fr. B11 (IC 50 =2.84 m The inhibitory activity of (g / mL) on breast cancer MDA-MB-232 cells was higher than that of the positive control cisplatin (IC50 g / mL). 50 =5.91 m g / mL). Fr. B2 (IC) 50 =0.57 m g / mL), Fr. B9 (IC 50 =0.86 mThe inhibitory activity of (g / mL) on colon cancer SW480 cells was significantly better than that of the positive control cisplatin (IC50 / mL). 50 =2.03 m g / mL). Fr. B2 (IC) 50 =2.77 m g / mL), Fr. B8 (IC 50 =0.31 m g / mL), Fr. B9 (IC 50 =0.30 m g / mL) and Fr. B11 (IC 50 =4.32 m The inhibitory activity of (g / mL) on NCI-H520 lung cancer cells was significantly higher than that of the positive control cisplatin (IC50 g / mL). 50 =5.39 m g / mL).

[0061] Table 3

[0062] Example 6: To investigate the inhibitory effects of compounds PGE90, PGE93a, PGE81, PGE82 and PGE83 on cancer cell growth.

[0063] Cancer cell cytotoxicity was assessed using the MTS method [Yang J, Hu DB, Xia MY, Luo JF, Li XY, Wang YH. Bioassay-guided isolation of cytotoxic constituents from the flowers of Aquilaria sinensis. Natural Products and Bioprospecting, 2022, 12, 1-11], with cisplatin and paclitaxel as positive controls. The results of the cytotoxicity assay are shown in Table 4 below. The IC50 values ​​of the dichloromethane extract (PXS272) of Aquilaria sinensis heartwood extract and the sesquiterpenoids isolated and identified therefrom inhibiting tumor cell growth are also presented. 50 The values ​​are shown in Table 4 below, and their activity was significantly higher than that of the positive control cisplatin. The new compounds PGE90, PGE93a, and PGE81 showed no significant inhibitory activity against leukemia HL-60 and K562 cells, lung cancer A549 cells, breast cancer MDA-MB-231 cells, and colon cancer SW480 cells. The known compounds PGE82 and PGE83 both showed good inhibitory activity, especially PGE82, which exhibited broad-spectrum inhibitory activity against the above five cell lines (IC50, 50%). 50 = 0.20-2.04 mTo further verify the broad-spectrum inhibitory activity of PGE82 against cancer cells, cytotoxic activity tests were performed on PGE82 in HepG2 liver cancer cells, HCT116 and Caco2 colon cancer cells, SK-OV-3 ovarian cancer cells, MG-63 osteosarcoma cells, and U251 glioblastoma cells. The results are shown in Table 5 below. The results indicate that PGE82 has significant cytotoxic activity against multiple cell lines, further verifying its broad-spectrum activity.

[0064] Table 4

[0065] Table 5

[0066] Example 7: The inhibitory effects of compounds PGE90, PGE93a, PGE81, PGE82 and PGE83 on the formation of nitric oxide (NO).

[0067] The anti-inflammatory test method is as follows: 1. Experimental Principle: Nitric oxide (NO) has broad and important biological regulatory functions, playing a crucial role in inflammation, tumors, and the cardiovascular system. When immune cells are stimulated by microbial endotoxins, inflammatory mediators, etc., they generate large amounts of induced NO synthase (iNOS), producing NO for the immune response. Therefore, inhibiting NO production is a direct indicator of the anti-inflammatory activity of compounds. Mouse RAW264.7 mononuclear macrophages were induced to produce nitric oxide synthase using LPS lipopolysaccharide, and the test compound was added simultaneously. The absorbance of the culture medium was measured at 570 nm using the Griess method to detect nitrite (NO). 2- ).

[0068] 2. Reagents: Mouse mononuclear macrophages RAW264.7 were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences. DMEM culture medium and fetal bovine serum were purchased from BI. Griess Reagent, lipopolysaccharide (LPS), and the positive control drug NG-monomethyl-L-arginine (L-NMMA) were purchased from Sigma.

[0069] 3. Experimental Methods: RAW264.7 cells were seeded into 96-well plates and treated with 1... m Induction stimulation was performed using g / ml LPS, while simultaneously adding the analytes (PGE90, PGE93a, PGE81, PGE82, and PGE83) (final concentration starting from 50 g / ml LPS). mCells were initially treated with a 2-fold dilution (M), and two control groups were set up: a drug-free group and an L-NMMA-positive drug group. After overnight culture, the culture medium was collected to detect NO production, and the absorbance was measured at 570 nm. MTS was added to the remaining culture medium to detect cell viability and rule out the toxic effects of the compound on cells.

[0070] NO generation inhibition rate (%) = (OD in non-drug treatment group) 570 nm - Sample group OD 570 nm ) / Non-drug treatment group OD 570 nm × 100% IC 50 (50% concentration of inhibition) calculated according to the Reed & Muench method.

[0071] The anti-inflammatory effects of PGE90, PGE93a, PGE81, PGE82, and PGE83 are shown in Table 6. As can be seen from the table, the anti-inflammatory effects of compounds PGE81, PGE82, and PGE83 are significantly better than those of the positive control drug L-NMMA.

[0072] Table 6 L-NMMA 50 54.02 ± 0.83 39.71 ± 0.19 25 41.89 ± 1.90 12.5 26.71 ± 2.49 6.25 14.62 ± 2.29 3.125 9.55 ± 1.57 PGE90 50 12.28 ± 1.45 – PGE93 50 6.25 ± 1.59 – PGE81 50 86.57 ± 2.91 25.65±0.81 25 48.64 ± 1.69 12.5 19.01 ± 2.55 6.25 7.60 ± 2.91 3.125 6.13 ± 2.37 PGE82 <![CDATA[50 1） ]]> 94.10± 1.46 9 0.19 ± 0.00 <![CDATA[25 1） ]]> 97.02 ± 0.27 <![CDATA[12.5 1） ]]> 98.35 ± 0.63 <![CDATA[6.25 1） ]]> 97.65 ± 1.72 <![CDATA[3.125 1） ]]> 99.72 ± 0.16 <![CDATA[1.56 1） ]]> 99.16 ± 0.28 <![CDATA[0.78 1） ]]> 98.25 ± 0.62 0.39 74.00 ± 1.28 0.2 51.35 ± 0.38 0.1 26.57 ± 1.85 PGE83 <![CDATA[50 1） ]]> 99.96 ± 0.22 10.19 ± 0.50 <![CDATA[25 1） ]]> 100.28 ± 0.42 12.5 61.98 ± 2.43 6.25 21.26 ± 4.10 3.125 2.31 ± 2.69 1.56 -7.64± 2.69 0.78 -12.37± 3.66 Note: " in Table 6 above 1) This indicates that the compound is cytotoxic at this concentration; "–" indicates that the inhibition rate did not exceed 50%, and IC testing was not continued. 50 value.

[0073] The above description is merely a preferred embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention are included within the scope of protection of the present invention.

Claims

1. A sesquiterpene compound, characterized in that, The sesquiterpenoids are selected from compounds represented by formulas A, B, C, D, and E: 。 2. A method for extracting sesquiterpenoid compounds, characterized in that, It is extracted from the heartwood of agarwood, and the specific steps include the following: (1) Take the heartwood of Aquilaria sinensis and crush it into powder. Add ethanol and extract it by ultrasonic extraction 6-8 times. The liquid is recovered under reduced pressure and concentrated to obtain the ethanol extract for later use. (2) Dissolve the ethanol extract in water and extract it 3-5 times in sequence with equal volumes of petroleum ether, dichloromethane, ethyl acetate and n-butanol to obtain the petroleum ether fraction, dichloromethane fraction, ethyl acetate fraction, n-butanol fraction and water fraction respectively. (3) The dichloromethane fraction was separated and extracted stepwise to obtain sesquiterpenoid compounds with different structures.

3. The method for extracting sesquiterpenoids according to claim 2, characterized in that, The volume fraction of ethanol mentioned in step (1) is 90%; the ultrasonic extraction is specifically performed under a water bath at 60°C.

4. The method for extracting sesquiterpenoids according to claim 2, characterized in that, The stepwise separation and extraction described in step (3) is to obtain the five sesquiterpene compounds with different structures as described in claim 1. Specifically, the compound corresponding to formula A is (7S,9S,10S)-9,11-dihydroxyeucalyptol-4-en-3-one; the compound corresponding to formula B is (7R,10S)-12,15-dihydroxyeucalyptol-4,11(13)-dien-3-one; the compound corresponding to formula C is (4S,5R,7R,10S)-5,11-epoxy-4-hydroxyeucalyptol-15-aldehyde; the compound corresponding to formula D is 12,15-dioxo-α-ostrichene; and the compound corresponding to formula E is ostrich-4,11(13)-dien-12,15-dialdehyde.

5. The method for extracting sesquiterpenoids according to claim 2, characterized in that, The specific operation of step-by-step separation and extraction described in step (3) is as follows: 1) The dichloromethane fraction was separated by silica gel column chromatography, yielding 12 fractions, labeled as Fr.B1-Fr.B12; 2) The Fr. B2 fraction was subjected to C18 reversed-phase silica gel column chromatography and eluted with methanol-water gradient to obtain 9 fractions, labeled as Fr.B2-1 ~ Fr.B2-9; 3) Fr. B2-3 was separated into two fractions using a Sephadex LH-20 gel chromatography column, which were labeled as Fr. B2-3-1 and Fr. B2-3-2 respectively; 4) Fr. B2-3-2 was divided by normal phase silica gel column chromatography and eluted with a gradient of petroleum ether-ethyl acetate system to obtain compounds PGE81, PGE82 and PGE83; 5) Fr. B10 was subjected to RP-18 reversed-phase silica gel column chromatography and eluted with methanol-water gradient to obtain 14 fractions, labeled as Fr. B10-1 ~ Fr. B10-14; 6) Fr. B10-2 was recrystallized from methanol to obtain two parts: Fr. B10-2-1 and Fr. B10-2-2. 7) Fr. B10-2-2 was further separated by elution with a concentration gradient of petroleum ether-acetone system using a normal-phase silica gel column to obtain a total of 12 fractions, Fr. B10-2-2-1 to Fr. B10-2-2-12; 8) Fr. B10-2-2-4 was separated into four fractions, Fr. B10-2-2-4-1 to Fr. B10-2-2-4-4, by Sephadex LH-20 gel chromatography; 9) Fr. B10-2-2-4-1 was separated by normal phase silica gel column chromatography and eluted with a dichloromethane-acetone system to obtain 6 fractions Fr. B10-2-2-4-1-1 ~ Fr. B10-2-2-4-6; 10) Fr. B10-2-2-4-1-4 was separated by semi-preparative HPLC to obtain two fractions: compound PGE90 and Fr. B10-2-2-4-1-4-2; 11) Fr. B10-2-2-4-1-4-2 was further separated by reverse-phase semi-preparative HPLC to obtain compound PGE93a.

6. The method for extracting sesquiterpenoids according to claim 5, characterized in that, In step 1), the chromatographic separation is performed using a petroleum ether-ethyl acetate system with a gradient of 20:1-0:1; in step 2), the methanol-water system has a gradient of 50%-100%; in step 4), the petroleum ether-ethyl acetate system has a gradient of 20:1; in step 5), the methanol-water system has a gradient of 30%-100%; in step 7), the normal-phase silica gel column is 200-300 mesh, and the petroleum ether-acetone system has gradients of 9:1, 3:1, 2:1, 1:1, and 0:1; in step 9), the dichloromethane-acetone system has gradients of 20:1, 15:1, 10:1, 5:1, and 3:

1.

7. The method for extracting sesquiterpenoids according to claim 5, characterized in that, In step 10), the semi-preparative HPLC column is 4.6 × 250 mm, the eluent is n-hexane-isopropanol with a ratio of 90:10, and the flow rate is controlled at 1 mL / min; in step 11), the semi-preparative HPLC column is 4.6 × 250 mm, the eluent is acetonitrile-water with a ratio of 20:70, and the flow rate is controlled at 1 mL / min.

8. The application of a sesquiterpene compound, characterized in that, The sesquiterpenoids are used in drugs for the prevention and treatment of leukemia, lung cancer, breast cancer, colon cancer, and inflammation.

9. The application of a sesquiterpene compound according to claim 8, characterized in that, The sesquiterpenoid compound is at least one of the following: (7S,9S,10S)-9,11-dihydroxyeucalyptol-4-en-3-one corresponding to Formula A; (7R,10S)-12,15-dihydroxyeucalyptol-4,11(13)-dien-3-one corresponding to Formula B; (4S,5R,7R,10S)-5,11-epoxy-4-hydroxyeucalyptol-15-aldehyde corresponding to Formula C; 12,15-dioxo-α-ostrichene corresponding to Formula D; and ostrichene-4,11(13)-dien-12,15-dialdehyde corresponding to Formula E.

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