Use of a 1,5-diphenylpent-1,4-dien-3-one compound in the preparation of an anti-schistosome drug

Abstract

The application belongs to the technical field of medicine, and particularly relates to application of a 1,5-diphenylpent-1,4-diene-3-ketone compound in preparation of an anti-schistosome drug. The 1,5-diphenylpent-1,4-diene-3-ketone compound has a structure shown in formula 1. The 1,5-diphenylpent-1,4-diene-3-ketone compound with the structure shown in formula 1 provided in the application has an unsaturated carbonyl structural unit (Michael acceptor unit) and a benzene ring structure, and the intermediate chain segment connecting the benzene ring structure and the Michael acceptor unit is short, which not only improves the anti-schistosome activity, but also enhances the structural stability and improves the bioavailability. Meanwhile, the 1,5-diphenylpent-1,4-diene-3-ketone compound provided in the application has low toxicity, can repair the liver damage of a host caused by schistosome infection to a certain extent, reduces the degree of liver fibrosis, and has strong protection on the host.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to the application of a 1,5-diphenylpentan-1,4-diene-3-one compound in the preparation of anti-schistosomiasis drugs. Background Technology

[0002] Schistosomiasis is an important, long-neglected tropical parasitic disease, second only to malaria. It is an epidemic caused by infection with three main schistosomes (Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum).

[0003] Currently, chemical drugs remain the primary method for treating schistosomiasis. Since Kikuth et al. began systematic research on drugs for treating schistosomiasis in the mid-1920s, dozens of chemotherapeutic drugs with insecticidal activity have emerged. However, only a few, such as praziquantel and oxaniquine, have been commercially produced. Praziquantel is currently the only drug used to prevent and treat various schistosomiasis infections in humans and animals. However, due to its extensive and long-term use, drug resistance has developed. According to the World Health Organization, 200 million people worldwide are infected with schistosomiasis, approximately 600 million are at risk of infection, 20 million have a high incidence rate, and at least 280,000 people die from schistosomiasis each year. In my country, areas where schistosomiasis transmission is not yet controlled are concentrated in marshy and mountainous regions with numerous animal hosts, widespread distribution of Oncomelania snails, and significant environmental influences, making prevention and control particularly difficult, and reinfection remains a serious problem.

[0004] Given the large number of people infected with schistosomiasis, relying solely on praziquantel as a chemical drug is disproportionate. Therefore, finding other or alternative anti-schistosomiasis drugs has become a public health priority. Summary of the Invention

[0005] The purpose of this invention is to provide an application of 1,5-diphenylpent-1,4-diene-3-one compounds in the preparation of anti-schistosomiasis drugs. The 1,5-diphenylpent-1,4-diene-3-one compounds with the structure shown in Formula 1 provided by this invention have strong anti-schistosomiasis activity, good biocompatibility and low toxicity, and can repair liver fibrosis in the host.

[0006] To achieve the above objectives, the present invention provides the following technical solution:

[0007] This invention provides the application of 1,5-diphenylpentan-1,4-dien-3-one compounds in the preparation of anti-schistosomiasis drugs, wherein the 1,5-diphenylpentan-1,4-dien-3-one compounds have the structure shown in Formula 1:

[0008]

[0009] In Formula 1: R is one or more of hydroxyl, alkoxy, halogen and haloalkyl; n is an integer from 0 to 5.

[0010] Preferably, R is one or more of hydroxyl, methoxy, halogen and halomethyl.

[0011] Preferably, R is one or more of hydroxyl, methoxy, fluorine, bromine, chlorine and CF3.

[0012] Preferably, the 1,5-diphenylpentan-1,4-dien-3-one compound has any one of the following structures:

[0013]

[0014] Preferably, the method for preparing the 1,5-diphenylpentan-1,4-dien-3-one compound includes the following steps:

[0015] The compound with the structure shown in Formula 2, acetone, organic solvent and inorganic strong acid were mixed and subjected to amide condensation reaction to obtain 1,5-diphenylpent-1,4-dien-3-one compounds with the structure shown in Formula 1.

[0016] In Formula 2: R is one or more of hydroxyl, alkoxy, halogen and haloalkyl; n is an integer from 0 to 3.

[0017] Preferably, the molar ratio of the compound with the structure shown in Formula 2 to acetone is 2:1.

[0018] Preferably, the inorganic strong acid is hydrochloric acid, and the mass content of HCl in the hydrochloric acid is 36-38%.

[0019] Preferably, after the amide condensation reaction is completed, the amide condensation reaction solution is obtained, and the reaction further includes: adjusting the pH of the amide condensation reaction solution to neutral, extracting the obtained neutral reaction solution with dichloromethane, combining the organic phases, and then sequentially drying, concentrating, and purifying by column chromatography to obtain a pure product of the 1,5-diphenylpentan-1,4-dien-3-one compound with the structure shown in Formula 1. The eluent used in the column chromatography purification is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is (1-15):1.

[0020] This invention provides an anti-schistosomiasis drug comprising a 1,5-diphenylpentan-1,4-dien-3-one compound with the structure shown in Formula 1 and a pharmaceutically acceptable carrier;

[0021]

[0022] In Formula 1: R is one or more of hydroxyl, alkoxy, halogen and haloalkyl; n is an integer from 0 to 5.

[0023] Preferably, the dosage form of the antischistosomiasis drug includes tablets, capsules, granules, oral liquids, or injections.

[0024] This invention provides the application of 1,5-diphenylpentan-1,4-dien-3-one compounds in the preparation of antischistosomiasis drugs, wherein the 1,5-diphenylpentan-1,4-dien-3-one compounds have the structure shown in Formula 1. The 1,5-diphenylpentan-1,4-dien-3-one compounds with the structure shown in Formula 1 provided by this invention have an unsaturated carbonyl structural unit (Michael acceptor unit) and a benzene ring structure, and the intermediate chain segment connecting the benzene ring structure to the Michael acceptor unit is relatively short, which not only improves its antischistosomiasis activity but also enhances its structural stability and improves its bioavailability. Simultaneously, the 1,5-diphenylpentan-1,4-dien-3-one compounds provided by this invention have low toxicity and can repair, to a certain extent, the liver damage caused by schistosomiasis infection in the host, reduce the degree of liver fibrosis, and have a certain protective effect on the host. The results of the examples show that this invention has screened compounds with high in vitro antischistosomiasis activity through in vitro antischistosomiasis activity screening. Furthermore, based on preliminary safety evaluation results, the in vivo anti-schistosomiasis activity and protective effect on the major organ (liver) of 1,5-diphenylpentane-1,4-dien-3-one compounds were evaluated. The results showed that the monocarbonyl bisMichael addition receptor 1,5-diphenylpentane-1,4-dien-3-one compounds provided in this invention can effectively enhance anti-schistosomiasis activity, with methoxy, hydroxyl, and fluorine substituents contributing to the enhanced activity, and position 4 being the most effective. Five compounds with strong anti-schistosomiasis activity were identified: 4-hydroxy (B3), 3,4-dimethyl (B5), 3,4,5-trimethoxy (B6), 4-fluoro (B8), and 3,4-difluoro (B13). Further investigation revealed that B5, B6, and B8 exhibited good biocompatibility and low toxicity. In particular, B5, administered at 500 mg / kg for 5 consecutive days to positive mice for 28 days, reduced the parasite load by 50.3%, decreased the liver oviposition rate by 42.8%, and the small intestinal oviposition rate by 84.6%. Simultaneously, B5 could protect the liver of positive mice to some extent, reducing liver fibrosis and demonstrating a certain degree of host protection, significantly superior to praziquantel (PZQ), which did not show significant anti-fibrotic activity at this time. Attached Figure Description

[0025] Figure 1 The flowchart shows the preparation process of the 1,5-diphenylpentane-1,4-diene-3-one compounds provided in the examples.

[0026] Figure 2 The graph shows the antischistosomiasis activity results of compounds B1, B2, B3 and B4 prepared for the examples;

[0027] Figure 3 The results of the antischistosomiasis activity of compounds B5, B6, B7 and B8 prepared for the examples are shown in the figure.

[0028] Figure 4 The results of the antischistosomiasis activity of compounds B9, B10, B11 and B12 prepared for the examples are shown in the figure.

[0029] Figure 5 The antischistosomiasis activity results of compounds B13, B14, B15 and B16 prepared for the examples are shown in the figure.

[0030] Figure 6 The effects of cisplatin, compound B3, compound B5, compound B6, compound B8 and compound B13 on the survival and growth of L929 cells;

[0031] Figure 7 The changes in liver and spleen indices after gavage administration of compounds B5, B6, and B8 in in vivo experiments;

[0032] Figure 8 Pathological sections of liver tissue from mice in vivo (×100);

[0033] Figure 9 The changes in hydroxyproline in the liver of mice after treatment with compound B5. Detailed Implementation

[0034] This invention provides the application of 1,5-diphenylpentan-1,4-dien-3-one compounds in the preparation of anti-schistosomiasis drugs, wherein the 1,5-diphenylpentan-1,4-dien-3-one compounds have the structure shown in Formula 1:

[0035]

[0036] In Formula 1: R is one or more of hydroxyl, alkoxy, halogen and haloalkyl; n is an integer from 0 to 5.

[0037] In this invention, unless otherwise specified, all raw materials / components used in the preparation are commercially available products well known to those skilled in the art.

[0038] In this invention, in Formula 1: R is preferably one or more of hydroxyl, methoxy, halogen and halomethyl, more preferably one or more of hydroxyl, methoxy, fluorine, bromine, chlorine and CF3, further preferably hydroxyl, methoxy, fluorine, bromine, chlorine or CF3, and most preferably hydroxyl, methoxy or fluorine.

[0039] In this invention, n is preferably an integer from 0 to 3, and more preferably an integer from 1 to 3.

[0040] In this invention, the 1,5-diphenylpentan-1,4-dien-3-one compounds preferably have any one of the following structures:

[0041]

[0042] In this invention, the 1,5-diphenylpentan-1,4-dien-3-one compound is more preferably B3, B5, B6, B8 or B13, further preferably B5, B6 or B8, and most preferably B5.

[0043] In this invention, the preparation method of the 1,5-diphenylpentan-1,4-dien-3-one compound preferably includes the following steps:

[0044] The compound with the structure shown in Formula 2, acetone, organic solvent and inorganic strong acid were mixed and subjected to amide condensation reaction to obtain 1,5-diphenylpent-1,4-dien-3-one compounds with the structure shown in Formula 1.

[0045] In Formula 2: R is one or more of hydroxyl, alkoxy, halogen and haloalkyl; n is an integer from 0 to 5.

[0046] In this invention, the organic solvent is preferably ethanol. The inorganic strong acid is preferably hydrochloric acid, and the mass content of HCl in the hydrochloric acid is preferably 36-38%. The molar ratio of the compound with the structure shown in Formula 2 to acetone is preferably 2:1. The mass ratio of acetone to the volume ratio of the inorganic strong acid is preferably 0.29 g: 5 mL. This invention does not have special requirements on the amount of the organic solvent used, as long as the aldol condensation reaction proceeds smoothly. The mixing preferably includes: dissolving the compound with the structure shown in Formula 2 and acetone in the organic solvent to obtain a mixed solution; mixing the mixed solution with the inorganic strong acid. The temperature of the amide condensation reaction is preferably room temperature, the time is preferably 6 hours, and the aldol condensation reaction is carried out under stirring. In this invention, after the aldol condensation reaction is completed, an amide condensation reaction solution is obtained. Preferably, this invention further includes: adjusting the pH of the aldol condensation reaction solution to neutral, extracting the obtained neutral reaction solution with dichloromethane, combining the organic phases, and then sequentially drying, concentrating, and purifying by column chromatography to obtain a pure product of a 1,5-diphenylpentan-1,4-dien-3-one compound with the structure shown in Formula 1. The eluent used in the column chromatography purification is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is preferably (1-15):1, specifically preferably 10:1, 2:1, 5:1, 1:1, or 15:1.

[0047] This invention provides an anti-schistosomiasis drug comprising a 1,5-diphenylpentan-1,4-dien-3-one compound with the structure shown in Formula 1 and a pharmaceutically acceptable carrier;

[0048]

[0049] In Formula 1: R is one or more of hydroxyl, alkoxy, halogen and haloalkyl; n is an integer from 0 to 5.

[0050] In this invention, the dosage form of the antischistosomiasis drug preferably includes tablets, capsules, granules, oral liquids, or injections.

[0051] To further illustrate the present invention, the technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0052] The following embodiments are all in accordance with Figure 1 The preparation was carried out according to the process shown. Some of the chemical reagents used in the following examples—2,4,6-trimethoxybenzaldehyde, 4-bromobenzaldehyde, 2-fluorobenzaldehyde, 3-2-fluorobenzaldehyde, 3,4-difluorobenzaldehyde, 2-methylbenzaldehyde, and 2-trifluoromethylbenzaldehyde—were purchased from Aladdin Reagent Co., Ltd. Ethanol, acetone, and concentrated hydrochloric acid were purchased from Xilong Scientific Co., Ltd. All the above reagents were of analytical grade; other reagents were chemically pure.

[0053] Example 1

[0054] 1.06 g (10 mmol) of benzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 10:1) to give a pale yellow solid B1. Melting point: 117.0–117.9 °C, yield: 54.7%.

[0055] 1 H NMR (400MHz, Chloroform-d) δ7.77(d,J=16.0Hz,2H),7.64-7.61(m,4H),7.44(qd,J=3.6,1.6Hz,6H),7.11(d,J=16.0Hz,2H). 13 C NMR(101MHz,Chloroform-d)δ189.02,143.43,134.93,130.61,129.09,128.51,125.56.HPLC-MS(ESI+ ):Calcd for C 17 H 15 O + [M+H] + 235.11174, found 235.11065.

[0056] Example 2

[0057] 1.52 g (10 mmol) of 4-hydroxy-3-methoxybenzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 2:1) to give a yellow solid B₂. Melting point: 73.3–77.7 °C, yield: 30.1%.

[0058] 1 H NMR (400MHz, DMSO-d6) δ9.66(s,2H),7.67(d,J=16.0Hz,2H),7.37(d,J=2.0Hz,2H),7. 21(dd,J=8.0,1.8Hz,2H),7.13(d,J=16.0Hz,2H),6.84(d,J=8.0Hz,2H),3.85(s,6H). 13 C NMR (101MHz, DMSO-d6) δ188.01,149.41,147.97,142.75,126.35,123.34,123.02,115.67,111.42,79.17,55.73. HPLC-MS (ESI - ):Calcd for C 19 H 17 O5 - [MH] - 325.10815, found 325.10811.

[0059] Example 3

[0060] 1.22 g (10 mmol) of 4-hydroxybenzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 2:1) to give a yellow solid B3. Melting point: 219.5–236.3 °C, yield: 33.4%.

[0061] 1 H NMR (400MHz, DMSO-d6) δ10.03(s,2H),7.68(d,J=16.0Hz,2H),7.63(d,J=8.6Hz,4H),7.12(d,J=15.9Hz,2H),6.85(d,J=8.6Hz,4H). 13 CNMR(101MHz,DMSO-d6)δ188.03,159.83,142.38,130.44,125.85,122.69,115.85.HPLC-MS(ESI-):Calcd forC 16 H 12 O - [M+HCOO] - 265.08702, found265.08639.

[0062] Example 4

[0063] 1.36 g (10 mmol) of anisaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 5:1) to give a pale yellow solid B4. Melting point: 117.5–120.7 °C, yield: 40.7%.

[0064] 1 H NMR (400MHz, Chloroform-d) δ7.72(d,J=16.0Hz,2H),7.58(d,J=8.7Hz,4H),6.97(d,J=16.0Hz,2H),6.92(d,J=8.7Hz,4H),3.85(s,6H). 13CNMR(101MHz,Chloroform-d)δ188.96,161.69,142.79,130.20,127.79,123.65,114.55,55.54.HPLC-MS(ESI + ):Calcdfor C 19 H 19 O3 + [M+H] + 295.13287, found 295.13201.

[0065] Example 5

[0066] 1.66 g (10 mmol) of 3,4-dimethoxybenzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 2:1) to give a pale yellow solid B5. Melting point: 110.4–120.6 °C, yield: 59.7%.

[0067] 1 H NMR(400MHz,DMSO-d6)δ7.72(d,J=16.0Hz,2H),7.41(d,J=1.8Hz,2H),7.33-7.3 1(m,2H),7.25(d,J=16.0Hz,2H),7.04(d,J=8.4Hz,2H),3.84(d,J=12.0Hz,12H). 13 CNMR(101MHz,DMSO-d6)δ188.07,151.06,149.01,142.55,127.57,123.79,123.19,111.64,110.52,55.62,55.57.HPLC-MS(ESI + ):Calcd for C 21 H 23 O5 + [M+H] + 355.15400, found 355.15352.

[0068] Example 6

[0069] 1.96 g (10 mmol) of 3,4,5-trimethoxybenzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 2:1) to give a bright yellow solid B6. Melting point: 69.4–71.0 °C, yield: 43.2%.

[0070] 1 H NMR (400MHz, Chloroform-d) δ7.68 (d, J = 16.0Hz, 2H), 7.00 (d, J = 16.0Hz, 2H), 6.85 (s, 4H), 3.92 (s, 12H), 3.90 (s, 6H). 13 C NMR(101MHz,Chloroform-d)δ188.60,153.61,143.46,140.61,130.39,124.91,105.81,61.11,56.35.HPLC-MS(ESI + ):Calcd forC 23 H 27 O7 + [M+H] + 415.17513, found 415.17429.

[0071] Example 7

[0072] 1.96 g (10 mmol) of 2,4,6-trimethoxybenzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 1:1) to give a yellow solid B7. Melting point: 148.7–156.5 °C, yield: 30.2%.

[0073] 1 H NMR (400MHz, Chloroform-d) δ8.16(d,J=16.0Hz,2H),7.50(d,J=16.0Hz,2H),6.14(s,4H),3.90(s,12H),3.85(s,6H). 13C NMR(101MHz,Chloroform-d)δ192.59,162.70,161.46,133.31,126.64,106.75,90.62,55.81,55.43.HPLC-MS(ESI + ):Calcd forC 23 H 27 O7 + [M+H] + 415.17513, found 415.17501.

[0074] Example 8

[0075] 1.24 g (10 mmol) of 4-fluorobenzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 10:1) to give a pale yellow solid B8. Melting point: 151.8–153.10 °C, yield: 33.2%.

[0076] 1 H NMR (400MHz, Chloroform-d) δ7.72 (d, J = 16.0Hz, 2H), 7.63-7.58 (m, 4H), 7.14-7.08 (m, 4H), 7.01 (d, J = 16.0Hz, 2H). 13 C NMR (101MHz, Chloroform-d) δ188.55,165.44,162.94,142.19,131.16,131.13,130.44,130.36,125.25,125.23,116.39,116.17. HPLC-MS (ESI + ):Calcd for C 17 H 13 F2O + [M+H] + 271.09290, found 271.09246.

[0077] Example 9

[0078] 1.40 g (10 mmol) of 4-chlorobenzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 15:1) to give a yellow solid B9. Melting point: 193.1–195.9 °C, yield: 65.2%.

[0079] 1 H NMR (400MHz, Chloroform-d) δ7.70 (d, J = 16.0Hz, 2H), 7.56-7.53 (m, 4H), 7.41-7.38 (m, 4H), 7.05 (d, J = 16.0Hz, 2H). 13 C NMR(101MHz,Chloroform-d)δ188.42,142.14,136.65,133.39,129.66,129.42,125.89.HPLC-MS(ESI + ):Calcd for C 17 H 13 Cl2O + [M+H] + 303.03380, found 303.03326.

[0080] Example 10

[0081] 1.84 g (10 mmol) of 4-bromobenzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 15:1) to give a pale yellow solid B10. Melting point: 214.2–215.7 °C, yield: 35.7%.

[0082] 1 H NMR (400MHz, Chloroform-d) δ7.68 (d, J = 16.0 Hz, 2H), 7.56 (d, J = 8.5 Hz, 4H), 7.48 (d, J = 8.5 Hz, 4H), 7.06 (d, J = 16.0 Hz, 2H). 13C NMR(101MHz,Chloroform-d)δ188.45,142.27,133.78,132.39,129.88,125.93,125.03.HPLC-MS(ESI + ):Calcd for C 17 H 13 Br2O + [M + ]390.93277,found 390.93152.

[0083] Example 11

[0084] 1.24 g (10 mmol) of 2-fluorobenzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 15:1) to give a pale yellow solid B11. Melting point: 71.4–75.1 °C, yield: 45.7%.

[0085] 1 H NMR (400MHz, DMSO-d6) δ835-8.28 (m, 4H), 7.94-7.89 (m, 2H), 7.81 (d, J = 16.1Hz, 2H), 7.77-7.63 (m, 4H). 13 C NMR(101MHz,DMSO-d6)δ215.78,198.25,173.22,170.71,145.23,145.19,142.76,142.67,13 9.66,139.63,138.35,138.29,135.35,135.32,133.36,133.25,126.64,126.42.HPLC-MS(ESI + ):Calcd for C 17 H 12 F2NaO + [M+Na] + 293.07484, found 293.07450.

[0086] Example 12

[0087] 1.24 g (10 mmol) of 3-fluorobenzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 15:1) to give a pale yellow solid B12. Melting point: 90.8–97.1 °C, yield: 30.4%.

[0088] 1 H NMR (400MHz, Chloroform-d) δ7.71(d,J=15.9Hz,2H),7.42-7.37(m,4H),7.33-7.30(m,2H),7.14(dtd,J=9.1,4.9,2.6Hz,2H),7.07(d,J=15.9Hz,2H). 13 C NMR(101MHz,Chloroform-d)δ188.43,164.44,161.99,142.33,142.31,137.16,137.08, 130.72,130.64,126.51,124.66,124.63,117.70,117.48,114.74,114.52.HPLC-MS(ESI + ):Calcd for C 17 H 13 F2O + [M+H] + 271.09290, found 271.09249.

[0089] Example 13

[0090] 1.42 g (10 mmol) of 3,4-difluorobenzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 10:1) to give a pale yellow solid B13. Melting point: 157.9–158.8 °C, yield: 42.7%.

[0091] 1H NMR (400MHz, DMSO-d6) δ7.96 (ddd, J=11.8, 7.9, 1.8Hz, 2H), 7.77 (d, J=16.1Hz ,2H),7.64-7.61(m,2H),7.56(dt,J=10.3,8.5Hz,2H),7.34(d,J=16.1Hz,2H). 13 CNMR(101MHz,DMSO-d6)δ188.29,151.82(d),150.96(d),149.33(d),148.52(d),140.77,1 32.60(dd),126.72-126.42(m),126.37-125.98(m),118.06(dz),116.70(d).HPLC-MS(ESI + ):Calcd for C 17 H 11 F4O + [M+H] + 307.07405, found 307.07323.

[0092] Example 14

[0093] 1.36 g (10 mmol) of 2-methoxybenzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 10:1) to give a pale yellow solid, B14. Melting point: 122.8–126.2 °C, yield: 41.5%.

[0094] 1 H NMR (400MHz, DMSO-d6) δ8.00(d,J=16.0Hz,2H),7.80(d,J=8.0Hz,2H),7.45(t,J=8.0Hz ,2H),7.33(d,J=16.0Hz,2H),7.11(d,J=8.3Hz,2H),7.04(t,J=7.5Hz,2H),3.89(s,6H). 13 C NMR (101MHz, DMSO-d6) δ188.97,158.68,137.64,132.51,128.98,126.67,123.43,121.18,112.23,56.10.HPLC-MS(ESI + ):Calcd for C19 H 19 O3 + [M+H] + 295.13287, found 295.13218.

[0095] Example 15

[0096] 1.21 g (10 mmol) of 2-methylbenzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 15:1) to give a pale yellow solid B15. Melting point: 123.6–124.0 °C, yield: 18.3%.

[0097] 1 H NMR (400MHz, Chloroform-d) δ8.07(d,J=15.8Hz,2H),7.67(d,J=7.9Hz,2H),7.33-7.29(m,2H),7.24(t,J=7.6Hz,4H),7.02(d,J=15.8Hz,2H),2.49(s,6H). 13 C NMR(101MHz,Chloroform-d)δ189.03,141.02,138.33,133.95,131.02,130.32,126.84,126.55,126.49,19.99.HPLC-MS(ESI + ):Calcd for C 19 H 19 O + [M+H] + 285.12499, found 285.12481.

[0098] Example 16

[0099] 1.74 g (10 mmol) of 2-CF3-benzaldehyde and 0.29 g (5 mmol) of acetone were dissolved in 25 mL of ethanol. After the reactants were completely dissolved, 5 mL of concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was completed, the pH was adjusted to neutral with dilute NaOH solution (10 wt%), and the mixture was extracted with dichloromethane. The organic phases were combined, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by column chromatography (V petroleum ether:V ethyl acetate = 10:1) to give a pale yellow solid B16. Melting point: 129.6–132.9 °C, yield: 25.5%.

[0100] 1 H NMR(400MHz,Chloroform-d)δ8.13-8.08(m,2H),7.82(d,J=8.0Hz,2H),7.77(d,J =8.0Hz,2H),7.65(t,J=8.0Hz,2H),7.55(t,J=8.0Hz,2H),7.05(d,J=16.0Hz,2H). 13 C NMR(101MHz,DMSO-d6)δ187.56,137.32,137.30,133.04,132.79,132.77,130.53,129.86 ,128.42,127.63,127.34,126.30,126.25,126.19,126.14,125.43,122.71.HPLC-MS(ESI + ):Calcd for C 19 H 13 OF6 + [M+H] + 371.08651, found 371.08610.

[0101] Test Example 1: Anti-schistosomiasis activity of 1,5-diphenylpentane-1,4-diene-3-one compounds against adult schistosomiasis worms

[0102] Following the in vitro insecticidal test procedures for the compounds prepared in Examples 1-13, the anti-adult activity of 1,5-diphenylpent-1,4-dien-3-one compounds (B1-B13) was evaluated sequentially. RPMI 1640 medium was used as the negative control group, RPMI 1640 medium containing 1% DMSO was used as the solvent control group, and praziquantel (PZQ) was used as the positive control.

[0103] Preparation of culture medium: Prepare the culture medium by mixing RPMI 1640 medium (88%), penicillin-streptomycin (2%) and newborn calf serum (10%) in the appropriate proportions and store at 4°C for later use.

[0104] 1,5-Diphenylpentane-1,4-dien-3-one compounds (B1~B13) stock solution: Weigh 0.04 mmol of 1,5-diphenylpentane-1,4-dien-3-one compounds (B1~B13) and dissolve in 1 mL of DMSO to prepare a 0.04 μmol / L stock solution. For small amounts of compounds that cannot be completely dissolved, vortexing or sonication can be used to promote complete dissolution. Store at 4°C. Mix well before use and prepare the required concentration according to the appropriate ratio.

[0105] Medium containing 10% newborn calf serum was pre-added to 1980 μL of 24-well plates and incubated at 37°C with 5% CO2 for 30 min. Five pairs of active adult worms with intact body membranes were picked into each well, and then different concentrations of compound solutions (20 μL) were added. Changes in the worms were observed at regular intervals, such as whether the body membrane swelled, whether the worms were curved, and the degree of decrease in activity frequency. The experiment was repeated twice.

[0106] Experimental Groups:

[0107] Control group: RPMI 1640 medium containing only 10% newborn calf serum

[0108] Negative control group: Culture medium containing 2% DMSO RPMI 1640. The concentration of DMSO was the highest among all experimental groups.

[0109] Positive control group: PZQ, used at a concentration of 10 μM during the experiment.

[0110] Experimental group: Compound concentration used: 2.5-40 μM.

[0111] First, the anti-adult worm resistance of the skeletal structure 1,5-diphenylpentan-1,4-dien-3-one (B1) and its analog B2 were evaluated. Figure 2 In this context, A represents the anti-schistosomiasis activity of B1. Figure 2 The B in the text represents the anti-schistosomiasis activity of B2.

[0112] After co-incubation with 40 μM B1 or B2 for 36 hours, the mortality rate of adult worms was over 85%, reaching 100% after 72 hours. At a concentration reduced to 20 μM, the mortality rate reached over 65% after 48 hours of incubation, and adults were completely killed after 72 hours. Even after incubation at 10 μM for 72 hours, B1 and B2 still exhibited good anti-schistosomiasis activity. This indicates that the 1,5-diphenylpentan-1,4-dien-3-one skeleton is a promising anti-schistosomiasis skeleton structure that can be used for modification to discover more effective anti-schistosomiasis compounds.

[0113] Furthermore, this invention investigated the anti-schistosomiasis activity of B3 and B4. Figure 2 The C in the formula represents the anti-schistosomiasis activity of B3. Figure 2 The "D" in the formula represents the anti-schistosomiasis activity of B4. After incubation at 40 μM B3 for 24 hours, adult worm viability decreased sharply, and adults died completely after 48 hours. At 20 μM B4, 90% insecticidal effect was still maintained after 48 hours. Further reducing the concentration to 10 μM and incubating for 72 hours, it could still effectively reduce adult worm viability by more than 75%. 40 μM B4 achieved an 80% insecticidal rate after 72 hours.

[0114] To further enhance activity, this invention introduces one methoxy group (B5) at the ortho position of the methoxy group in B4, and two methoxy groups (B6 and B7) at the meta position. Figure 3 In this context, A represents the anti-schistosomiasis activity of B5. Figure 3 The B in the text refers to the anti-schistosomiasis activity of B6. Figure 3 C in the formula represents the anti-schistosomiasis activity of B7.

[0115] After incubation at 20 μM for 24 hours, B5 caused 80% mortality of adult worms, while B6 completely killed schistosomes after 72 hours of incubation. B7 showed a mortality rate of less than 50% at this time, exhibiting poor anti-parasitic effect. When the concentration was reduced to 10 μM, B6 also completely killed schistosomes after 72 hours of incubation. Figure 3 The results indicate that the overall insecticidal effect is: B6>B5>B4>B7, meaning that the insecticidal effect significantly improves with the increase of the number of methoxy groups.

[0116] This invention also introduced an F atom (B8) at the 4 position of the benzene ring to investigate its insecticidal activity, and at the same time investigated the activities of Cl and Br.

[0117] Figure 3 The D in the figure represents the anti-schistosomiasis activity of B8. Figure 4 In this context, A represents the anti-schistosomiasis activity of B9. Figure 4 The B in the figure represents the anti-schistosomiasis activity of B10.

[0118] At 20 μM for 72 h, B8 can completely kill schistosomes, B9 has a 50% kill rate, and B10 has a 30% kill rate. The activity order is B8>B9>B10, which is consistent with the electron-withdrawing ability of F, Cl, and Br. Strong electron-withdrawing substituents are beneficial to enhancing the anti-schistosome activity of the compound.

[0119] Meanwhile, the present invention also investigated the activity of ortho (B11) and meta (B12) F analogs, examined the effect of the position of F on the activity, and evaluated the insecticidal activity of B13 by increasing the amount of F. Figure 4 The C in the text represents the anti-schistosomiasis activity of B11. Figure 4 The D in the figure represents the anti-schistosomiasis activity of B12. Figure 5 In the figure, A represents the anti-schistosomiasis activity of B13. At 40-20 μM, after 24 hours of incubation, B11 and B12 completely killed adult schistosomiasis, while B10 at 20 μM for 72 hours completely killed it. At 10 μM, after 72 hours of incubation, B12 still completely killed schistosomiasis. Meanwhile, B13 showed better activity than B12, but was close to that of B8, indicating that increasing the number of F atoms can slightly improve the activity.

[0120] The present invention also investigated the anti-schistosomiasis activity of ortho-methoxy (B14), methyl (B15) and trifluoromethyl (B16). Figure 5The B in the text represents the anti-schistosomiasis activity of B14. Figure 5 The C in the text represents the anti-schistosomiasis activity of B15. Figure 5 D in the figure represents the anti-schistosomiasis activity of B16.

[0121] At 40 μM, B14 and B15 can completely kill adult worms after 48 hours of incubation. B14 can completely kill schistosomes at 20 μM for 48 hours. At 20 μM, B15 and B16 can completely kill schistosomes after 72 hours of incubation.

[0122] In summary, this invention reveals that 1,5-diphenylpentan-1,4-dien-3-one is a favorable anti-schistosomiasis skeleton, and that altering the type and position of substituents on the benzene ring can enhance its anti-schistosomiasis activity. Furthermore, the 4-position in the 1,5-diphenylpentan-1,4-dien-3-one skeleton is most conducive to antiparasitic activity, with methoxy, hydroxy, and fluorine substituents exhibiting even better anti-schistosomiasis activity. The lipophilicity of the compound, the number and position of substituents, and electronegativity collectively regulate the activity, with 4-hydroxy (B3), 3,4-dimethyl (B5), 3,4,5-trimethoxy (B6), 4-fluoro (B8), and 3,4-difluoro (B13) exhibiting the strongest anti-schistosomiasis activity. Therefore, subsequent in vivo anti-schistosomiasis activity studies will be conducted using B3, B5, B6, B8, and B13.

[0123] The in vitro anti-schistosomiasis activity of compounds B1-B16 prepared in Examples 1-16 was determined, and the adult mortality rate test results are shown in Table 1.

[0124] Table 1. In vitro antischistosomiasis activity of compounds B1-B16

[0125]

[0126]

[0127]

[0128] Test Example 2: Cytotoxicity Evaluation of 1,5-Diphenylpentane-1,4-diene-3-one Compounds

[0129] Compounds B3, B5, B6, B8, and B13, which exhibit high in vitro anti-schistosomiasis activity, were selected, and their cytotoxicity was evaluated using normal cells.

[0130] Using normal L929 cells (mouse epithelial fibroblasts) as the model cell, cisplatin was used. ] The experimental groups were B3, B5, B6, B8, and B13, serving as the positive control group. The toxicity of the compounds to normal cells was evaluated using 20 μM as the upper limit of concentration, which was the lowest concentration required for complete insecticidal activity. Figure 6The effects of cisplatin, vitamins B3, B5, B6, B8, and B13 on the survival and growth of L929 cells were investigated. At 20 μM for 48 h, the survival rate of L929 cells treated with B5, B6, and B8 was above 70%. At the same concentrations, the survival rate of L929 cells treated with B3 and B13 was below 40%. Figure 6 When the concentration was reduced to 5 μM, low concentrations of B5, B6, and B8 promoted cell growth, and the survival rate of L929 cells exceeded 100%. Figure 6 Therefore, within this concentration range, B5, B6, and B8 exhibit the least toxicity to normal cells. Thus, this invention selected B5, B6, and B8 for subsequent in vivo anti-schistosomiasis studies.

[0131] Test Example 3: In vivo anti-schistosomiasis effect of 1,5-diphenylpentane-1,4-diene-3-one compounds

[0132] Using schistosomiasis-infected positive mice as a model and PZQ as a positive control, the in vivo anti-schistosomiasis activity of B5, B6 and B8 was evaluated.

[0133] Mice were randomly divided into four groups: a blank control group (uninfected mice), a negative control group (infected but untreated mice), a positive control group (PZQ), and treatment groups (B5, B6, and B8), with five mice in each group. Mice were infected with cercariae for 28 days (adult stage) and then administered a 500 mg / kg dose by gavage for 5 consecutive days, followed by 14 days of standard feeding (a total of 47 days of feeding). The mice were then dissected. The number of adult worms parasitizing the portal vein and mesentery was counted, and the total number of worms, female worms, and male worms was calculated. Simultaneously, worm eggs on the liver and small intestine were counted. Due to space limitations, the experiment was conducted in two batches: negative control group 1 served as a control for PZQ, B5, and B6; negative control group 2 served as a control for B8.

[0134] The control group (normal mice) maintained normal health during the experiment. The negative control groups (Control 1 and Control 2) showed decreased activity, weight loss, and prickly hair during the experiment, but no mice died. Dissection revealed that adult worms were mainly concentrated in the portal vein and mesentery; no adult worms were found in other areas. The adult worms were highly active and relatively slender.

[0135] Mice treated with B5, B6, and B8 showed strong vitality during the observation period and did not exhibit weight loss or prickly hair. After 47 days, dissecting mice in the B5 treatment group revealed that adult worms were mainly concentrated in the portal vein and mesentery, with a total reduction rate of 50.3%; the oviposition rates in the liver and small intestine were 42.8% and 84.6%, respectively. In the B6 treatment group, most adult worms were concentrated in the portal vein, with a small portion in the mesentery, resulting in a total reduction rate of 36.2%; the oviposition rates in the liver and small intestine were 40.0% and 84.8%, respectively. In the B8 treatment group, a large number of adult worms were found in the portal vein and mesentery, with a total reduction rate of only 20.3%; the oviposition rates in the liver and small intestine were only 44.5% and 42.3%, respectively. Overall, the in vivo antiparasitic effects of B5, B6, and B8 were B5 > B6 > B8 (Table 2).

[0136] Table 2. In vivo killing effects of B5, B6, and B8 on 28-day-old adults.

[0137]

[0138]

[0139] a Control 1: Infected mice (untreated), PZQ, B5 and B6 controls; b Control 2: Infected mice (untreated), B8 control; c If no adult worms were found in the portal vein, mesentery, or other areas of mice, the group was designated as the complete treatment group. d On day 5 of gavage, the mice died. One mouse died abnormally, and the data was not collected. e The insect reduction rate is calculated using the corresponding average value.

[0140] Test Example 4: Protective Effect of 1,5-Diphenylpentane-1,4-dien-3-one Compounds on the Host

[0141] (1) Morphology of liver and spleen in mice after treatment with 1,5-diphenylpentan-1,4-dien-3-one compounds

[0142] Figure 7 The liver index of mice after oral administration of 500 mg / kg PZQ, B5, B6 and B8 respectively was measured. Figure 7 A) and spleen index ( Figure 7 Changes in B) in the liver and spleen indices were observed. Compared to the negative control, mice treated with B5, B6, and B8 showed varying degrees of reduction in liver and spleen indices, with B5 showing the best results. This is consistent with the fact that B5 has the best in vivo insecticidal activity.

[0143] (2) The anti-fibrotic effect of 1,5-diphenylpentan-1,4-dien-3-one compound B5 on mouse liver liver

[0144] Since B5 is the best analogue in this series for maintaining liver morphology, to clarify its anti-liver fibrosis ability, this invention further used pathological sections to observe the condition of the liver after B5 treatment, and simultaneously measured hydroxyproline, a typical indicator reflecting the metabolism and degree of fibrosis in liver and other tissues. The results were also compared with those of the liver treated with PZQ.

[0145] Figure 8 The images show histopathological sections of liver tissue from mice used in vivo (×100), and the blank control group (…). Figure 8 A in the middle), negative control group ( Figure 8 B in the middle), 500mg / kg PZQ ( Figure 8 C) and B5 ( Figure 8 (D in the text). H&E staining of liver sections showed that histological analysis of normal mouse livers revealed normal lobular structure, without pathological degeneration such as inflammation or vacuolar degeneration. Figure 8 In A), untreated mice (negative control group) had a large number of Schistosoma eggs in their livers, surrounded by inflammatory reactions and acute swelling of hepatocytes, with large areas of granulomas. Figure 8 (B in the text). After PZQ treatment, the number of parasite eggs in the liver of mice was significantly reduced, the inflammatory response and acute swelling were significantly relieved, and the number and size of granulomas were significantly reduced. Figure 8 The presence of C in the figure indicates that PZQ has a weak ability to repair liver tissue. After treatment with B5, there were no obvious parasite eggs, the area and number of granulomas were significantly reduced, the liver parenchyma was normal, and there was no inflammatory reaction in the portal areas. Figure 8 The result of D indicates that B5 treatment, to a certain extent, alleviated the pathological changes in the liver caused by schistosomiasis and had a certain protective effect on the liver.

[0146] Figure 9 This represents the change in hydroxyproline levels in the liver of mice after treatment with compound B5. Figure 9 It was found that the hydroxyproline level in the liver of mice treated with both PZQ and B5 decreased to some extent. After PZQ treatment, the hydroxyproline level was significantly higher than in the blank group and comparable to the control group, indicating that while PZQ could maintain liver morphology, it could not improve liver fibrosis. In mice treated with B5, the hydroxyproline level was significantly reduced, essentially reaching normal levels. This shows that B5 significantly improved the degree of liver fibrosis more effectively than PZQ, demonstrating the unique advantage of 1,5-diphenylpentan-1,4-dien-3-one compounds as anti-schistosomiasis drugs, exhibiting both anti-parasitic activity and significant organ protection and repair effects on the host. Figure 9 The changes in hydroxyproline in the liver of mice after treatment with B5.

[0147] This invention synthesized 1,5-diphenylpentan-1,4-dien-3-one compounds with the 1,5-diphenylpentan-1,4-dien-3-one skeleton, and investigated their anti-schistosomiasis activity in detail, screening out compounds with high in vitro anti-schistosomiasis activity. Five compounds with strong anti-schistosomiasis activity were discovered: 4-hydroxy (B3), 3,4-dimethyl (B5), 3,4,5-trimethoxy (B6), 4-fluoro (B8), and 3,4-difluoro (B13). Furthermore, B5, B6, and B8 were found to have good biocompatibility and low toxicity. In particular, B5 reduced the parasite load by 50.3% and the small intestinal egg reduction capacity by 84.6% in vivo. More importantly, B5 can protect the liver to a certain extent and reduce the degree of liver fibrosis, significantly better than PZQ, which did not show significant anti-fibrotic ability at this time.

[0148] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. Other embodiments can be obtained based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. The application of a 1,5-diphenylpentan-1,4-dien-3-one compound in the preparation of antischistosomiasis drugs, characterized in that, The 1,5-diphenylpentan-1,4-dien-3-one compounds have any one of the following structures: 、 。 2. The application according to claim 1, characterized in that, The dosage forms of the antischistosomiasis drugs include tablets, capsules, granules, oral liquids, or injections.

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