A curcumin analogue, its preparation method and application

Abstract

This invention provides a curcumin analogue, its preparation method, and its application, belonging to the field of biomedical technology. The curcumin analogue includes 1,7-bis(3-hydroxy-4-methoxyphenyl)-4-n-butyl-1,6-heptadien-3,5-dione, 1,7-bis(3-hydroxy-4-methoxyphenyl)-4-cyclopropylmethyl-1,6-heptadien-3,5-dione, and 1,7-bis(3-trifluoromethoxyphenyl)-4-n-butyl-1,6-heptadien-3,5-dione. The curcumin analogue provided by this invention can effectively inhibit renal fibrosis, with a significantly better therapeutic effect than curcumin alone, and has potential application value in the field of renal fibrosis treatment drugs.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to a curcumin analogue, its preparation method, and its application. Background Technology

[0002] Chronic kidney disease (CKD) has become a major global public health problem, with a global adult prevalence exceeding 10%. China has the highest number of patients in Asia, posing a serious threat to human health. Renal fibrosis is the core pathological pathway and common outcome of various chronic kidney diseases, such as diabetic nephropathy, hypertensive nephropathy, obstructive nephropathy, and lupus nephritis, progressing to end-stage renal disease (ESRD). Its pathological features include excessive deposition of extracellular matrix such as collagen and fibronectin in the renal interstitial cells, renal tubular atrophy, abnormal activation and proliferation of interstitial fibroblasts, and persistent infiltration of inflammatory cells. Ultimately, this leads to the destruction of kidney structure and irreversible loss of kidney function, requiring patients to rely on dialysis or kidney transplantation to maintain life, resulting in a heavy medical burden.

[0003] The current clinical treatment of renal fibrosis has fundamental flaws. Existing treatments mainly consist of ACEI / ARB antihypertensive drugs and hypoglycemic drugs, which can only slow down the decline in renal function but cannot block or reverse the fibrosis process.

[0004] Curcumin is a natural polyphenolic active ingredient extracted from the ginger plant *Curcuma longa* L., possessing multiple pharmacological activities including anti-inflammatory, antioxidant, anti-fibrotic, and immunomodulatory effects, demonstrating significant potential in the treatment of renal fibrosis. The core mechanisms of action of curcumin include: inhibiting the TGF-β1 / Smad2 / 3 core fibrosis pathway, reducing Smad2 / 3 phosphorylation and nuclear translocation, and blocking fibroblast activation and ECM synthesis; regulating the TLR4 / NF-κB and PI3K / Akt inflammatory signaling pathways, reducing the release of pro-inflammatory factors such as TNF-α, IL-1β, and IL-6, and alleviating renal interstitial inflammation; inhibiting renal tubular epithelial-mesenchymal transition (EMT), downregulating α-SMA and vimentin expression, and reversing epithelial cell phenotype loss; activating the Nrf2 antioxidant pathway, scavenging reactive oxygen species (ROS), and reducing oxidative stress damage; and regulating the circRNA / miRNA non-coding RNA axis, intervening in the expression of fibrosis-related genes. However, existing curcumin analogs still have key shortcomings. Most analogs only optimize solubility or stability, and have not achieved a qualitative breakthrough in the inhibitory strength of core pathways such as TGF-β / Smad and NF-κB, or in their renal targeting. Therefore, there is an urgent need to develop new curcumin analogs with stronger therapeutic effects on renal fibrosis. Summary of the Invention

[0005] To address the shortcomings of the prior art, this invention provides a curcumin analogue, its preparation method, and its applications. The curcumin analogue exhibits significantly better therapeutic effects on renal fibrosis than curcumin alone and can be used as an effective active ingredient in the preparation of drugs for treating renal fibrosis.

[0006] To achieve the above objectives, the specific technical solution of the present invention is as follows:

[0007] In a first aspect, the present invention provides a curcumin analogue, the structural formula of which is shown below:

[0008] ;

[0009] In the formula, R1 is a C3-C5 alkyl group, including straight-chain alkyl, branched alkyl or cycloalkyl; R2 is 3-hydroxy and 4-methoxy, or 3-trifluoromethoxy.

[0010] Further, R1 is propyl, isopropyl, n-butyl, cyclopropylmethyl, or isopentyl.

[0011] Furthermore, the structural formula of the curcumin analogue is shown in formula (I), (II), or (III):

[0012] (The Chinese name is: 1,7-bis(3-hydroxy-4-methoxyphenyl)-4-n-butyl-1,6-heptadiene-3,5-dione).

[0013] (The Chinese name is: 1,7-bis(3-hydroxy-4-methoxyphenyl)-4-cyclopropylmethyl-1,6-heptadiene-3,5-dione).

[0014] (The Chinese name is: 1,7-bis(3-trifluoromethoxyphenyl)-4-n-butyl-1,6-heptadien-3,5-dione).

[0015] Secondly, the present invention provides a method for preparing the curcumin analogue, the reaction formula of which is as follows:

[0016] ;

[0017] In the formula, R1 is a C3-C5 alkyl group, including straight-chain alkyl, branched alkyl, or cycloalkyl; R2 is 3-hydroxy and 4-methoxy, or 3-trifluoromethoxy; X is chlorine, bromine, or iodine;

[0018] The steps are as follows:

[0019] 2,4-pentanedione with haloalkanes ( Under alkaline conditions, a substitution reaction occurs to give 3-alkyl-2,4-pentanedione;

[0020] 3-alkyl-2,4-pentanedione and substituted benzaldehyde ( Under the conditions of boric acid, tributyl borate and n-butylamine, an aldol condensation reaction occurs to obtain curcumin analogues.

[0021] Furthermore, the alkaline conditions in the substitution reaction are provided by sodium carbonate or potassium carbonate; the solvent used in the substitution reaction is at least one of N,N-dimethylformamide, ethanol, and isopropanol.

[0022] Furthermore, the temperature of the substitution reaction is 60-90 °C.

[0023] Specifically, the substitution reaction is performed as follows: a base is added to a solvent to dissolve the base, and 2,4-pentanedione is added while stirring to obtain a mixture; a haloalkane is added to the above mixture, the temperature is raised to 60-90 °C and the reaction is carried out overnight, the solvent is removed, water is added to dissolve the residue, the residue is extracted with ethyl acetate, dried with magnesium sulfate, ethyl acetate is removed by vacuum distillation, and 3-alkyl-2,4-pentanedione is obtained by vacuum distillation.

[0024] Furthermore, the aldol condensation reaction is carried out at a temperature of 60-90 °C.

[0025] Furthermore, the solvent used in the aldol condensation reaction is at least one of N,N-dimethylformamide, tetrahydrofuran, and ethyl acetate.

[0026] Specifically, the aldol condensation reaction is performed as follows: 3-alkylmethyl-2,4-pentanedione and boric acid are dissolved in a solvent, heated to 60-90 °C and reacted for 10-30 minutes, then tributyl borate and substituted benzaldehyde are added, followed by n-butylamine. After reacting for 1-3 hours, an aqueous acetic acid solution is added and the reaction continues for another 1-3 hours. A solid is precipitated, cooled to room temperature, filtered, and recrystallized from methanol to obtain a curcumin analogue.

[0027] Thirdly, the present invention provides the use of the curcumin analogue in the preparation of a medicament for treating renal fibrosis.

[0028] Fourthly, the present invention provides a pharmaceutical composition for treating renal fibrosis, the pharmaceutical composition comprising the curcumin analogue.

[0029] Furthermore, the pharmaceutical composition further includes one or more pharmaceutically acceptable carriers or excipients.

[0030] Compared with the prior art, the advantages of the present invention are:

[0031] The curcumin analog provided by this invention can effectively inhibit renal fibrosis (Masson staining). In a mouse model of renal fibrosis, its therapeutic effect is significantly better than that of curcumin. It can be used as an active ingredient to prepare drugs for the treatment of renal fibrosis. Attached Figure Description

[0032] Figure 1 This is a schematic diagram illustrating the construction of the mouse renal fibrosis model and the drug administration strategy of this invention;

[0033] Figure 2 Masson staining images of mouse kidneys after treatment with the compounds prepared in Examples 1-3 of this invention for mouse renal fibrosis;

[0034] Figure 3 The proton NMR spectrum of the compound represented by formula (I) in Example 1 of this invention;

[0035] Figure 4 The carbon NMR spectrum of the compound shown in formula (I) in Example 1 of this invention;

[0036] Figure 5 The high-resolution mass spectrum of the compound shown in formula (I) in Example 1 of this invention;

[0037] Figure 6 The proton nuclear magnetic resonance spectrum of the compound shown in formula (II) in Example 2 of this invention;

[0038] Figure 7 The carbon NMR spectrum of the compound shown in formula (II) in Example 2 of this invention;

[0039] Figure 8 The high-resolution mass spectrum of the compound shown in formula (II) in Example 2 of this invention;

[0040] Figure 9 The proton nuclear magnetic resonance spectrum of the compound represented by formula (III) in Example 3 of this invention;

[0041] Figure 10 The carbon NMR spectrum of the compound shown in formula (III) in Example 3 of this invention;

[0042] Figure 11 This is a high-resolution mass spectrum of the compound shown in formula (III) in Example 3 of the present invention. Detailed Implementation

[0043] To enable those skilled in the art to clearly and completely understand the technical solution of the present invention, the present invention will be further described in detail below with reference to embodiments. Obviously, the embodiments described herein are only for explaining the present invention and are not intended to limit the scope of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0044] This invention provides a curcumin analogue, the structural formula of which is shown below:

[0045] ;

[0046] In the formula, R1 is a C3-C5 alkyl group, including straight-chain alkyl, branched alkyl or cycloalkyl; R2 is 3-hydroxy and 4-methoxy, or 3-trifluoromethoxy.

[0047] In some examples, R1 is propyl, isopropyl, n-butyl, cyclopropylmethyl, or isopentyl.

[0048] In some examples, the structural formulas of the curcumin analogues are shown in formulas (I), (II), or (III):

[0049] (The Chinese name is: 1,7-bis(3-hydroxy-4-methoxyphenyl)-4-n-butyl-1,6-heptadiene-3,5-dione).

[0050] (The Chinese name is: 1,7-bis(3-hydroxy-4-methoxyphenyl)-4-cyclopropylmethyl-1,6-heptadiene-3,5-dione).

[0051] (The Chinese name is: 1,7-bis(3-trifluoromethoxyphenyl)-4-n-butyl-1,6-heptadien-3,5-dione).

[0052] This invention also provides a method for preparing the curcumin analogue, the reaction formula of which is as follows:

[0053] ;

[0054] In the formula, R1 is a C3-C5 alkyl group, including straight-chain alkyl, branched alkyl, or cycloalkyl; R2 is 3-hydroxy and 4-methoxy, or 3-trifluoromethoxy; X is chlorine, bromine, or iodine;

[0055] The steps are as follows:

[0056] 2,4-pentanedione with haloalkanes ( Under alkaline conditions, a substitution reaction occurs to give 3-alkyl-2,4-pentanedione;

[0057] 3-alkyl-2,4-pentanedione and substituted benzaldehyde ( Under the conditions of boric acid, tributyl borate and n-butylamine, an aldol condensation reaction occurs to obtain curcumin analogues.

[0058] In some examples, the basic conditions in the substitution reaction are provided by sodium carbonate or potassium carbonate; the solvent used in the substitution reaction is at least one of N,N-dimethylformamide, ethanol, and isopropanol.

[0059] In some examples, the temperature of the substitution reaction is 60-90 °C.

[0060] In some examples, the aldol condensation reaction is carried out at a temperature of 60-90 °C.

[0061] In some examples, the solvent used in the aldol condensation reaction is at least one of N,N-dimethylformamide, tetrahydrofuran, and ethyl acetate.

[0062] Unless otherwise specified, the technical means used in the embodiments are conventional means well known to those skilled in the art. Unless otherwise specified, the reagents, methods and equipment used in this invention are conventional reagents, methods and equipment in the art.

[0063] Example 1

[0064] The preparation of the compound shown in formula (I) is carried out by the following reaction:

[0065] ;

[0066] The preparation steps are as follows:

[0067] (1) 6.9 g of potassium carbonate was added to 30 mL of isopropanol and stirred at room temperature for 20 minutes. Then 5 g of 2,4-pentanedione was added dropwise to obtain a mixture. 6 g of n-butyl bromide was dissolved in 10 mL of isopropanol and added dropwise to the above mixture. The mixture was heated to 60 °C and stirred overnight. Isopropanol was removed by vacuum distillation. 30 mL of water was added to dissolve the residue. Ethyl acetate was added and extracted three times, 20 mL each time. The organic phases were combined, dried with anhydrous magnesium sulfate, and ethyl acetate was removed by vacuum distillation. Finally, 3-n-butyl-2,4-pentanedione was obtained by vacuum distillation with a yield of 84%.

[0068] (2) Dissolve 3 g of 3-n-butyl-2,4-pentanedione and 0.7 g of boric acid in 15 mL of N,N-dimethylformamide and heat to 80 °C and reflux for 20 minutes; add 9 g of tributyl borate and 7 g of 3-hydroxy-4-methoxybenzaldehyde, then add 0.7 g of n-butylamine (dissolved in 5 mL of N,N-dimethylformamide), and continue to stir the reaction at 80 °C for 2 hours; add 100 mL of 20% acetic acid aqueous solution and continue to react for 2 hours, and a solid precipitates; cool the reaction solution to room temperature, filter, and recrystallize with methanol to obtain pure 1,7-bis(3-hydroxy-4-methoxyphenyl)-4-n-butyl-1,6-heptadien-3,5-dione with a yield of 76%.

[0069] like Figure 3-5 As shown, the characterization data for 1,7-bis(3-hydroxy-4-methoxyphenyl)-4-n-butyl-1,6-heptadien-3,5-dione are as follows:

[0070] 1H NMR (400 MHz, DMSO) δ 9.24 (d, J = 11.6 Hz, 2H), 7.56 (dd, J =15.7, 5.6 Hz, 2H), 7.41 – 7.09 (m, 4H), 7.09 – 6.85 (m, 3H), 6.77 (d, J =16.0 Hz, 1H), 4.53 (t, J = 6.9 Hz, 1H), 3.82 (d, J = 6.2 Hz, 6H), 2.61 (s,1H), 1.81 (q, J = 7.4 Hz, 1H), 1.51 – 1.36 (m, 2H), 1.25 (dt, J = 33.0, 7.7Hz, 2H), 0.90 (dt, J = 41.4, 6.9 Hz, 3H).

[0071] 13 C NMR (101 MHz, DMSO) δ 195.81, 183.03, 150.93, 150.49, 147.20,144.19, 141.82, 128.44, 127.42, 123.45, 122.50, 122.18, 118.52, 114.68,114.55, 112.48, 61.91, 56.13, 56.10, 29.75, 28.44, 22.64, 22.11, 14.45,14.28.

[0072] HRMS: m / z of [M+H] +Calculated for C 25 H 28 O6425.1964, found 425.1962.

[0073] Example 2

[0074] The preparation of the compound shown in formula (II) is carried out by the following reaction:

[0075] ;

[0076] The preparation steps are as follows:

[0077] (1) 6.9 g of potassium carbonate was added to 30 mL of isopropanol and stirred at room temperature for 20 minutes. Then 5 g of 2,4-pentanedione was added dropwise to obtain a mixture. 6 g of bromomethylcyclopropane was dissolved in 10 mL of isopropanol and added dropwise to the above mixture. The mixture was heated to 60 °C and stirred overnight. Isopropanol was removed by vacuum distillation. 30 mL of water was added to dissolve the residue. Ethyl acetate was added for extraction three times, 20 mL each time. The organic phases were combined, dried with anhydrous magnesium sulfate, and ethyl acetate was removed by vacuum distillation. Finally, 3-cyclopropylmethyl-2,4-pentanedione was obtained by vacuum distillation with a yield of 82%.

[0078] (2) Dissolve 3 g of 3-cyclopropylmethyl-2,4-pentanedione and 0.7 g of boric acid in 15 mL of N,N-dimethylformamide and heat to 80 °C and reflux for 20 minutes; add 9 g of tributyl borate and 7 g of 3-hydroxy-4-methoxybenzaldehyde, then add 0.7 g of n-butylamine (dissolved in 5 mL of N,N-dimethylformamide), and continue to stir the reaction at 80 °C for 2 hours; add 100 mL of 20% acetic acid aqueous solution and continue to react for 2 hours, and a solid precipitates; cool the reaction solution to room temperature, filter, and recrystallize with methanol to obtain pure 1,7-bis(3-hydroxy-4-methoxyphenyl)-4-cyclopropylmethyl-1,6-heptadien-3,5-dione with a yield of 75%.

[0079] like Figure 6-8 As shown, the characterization data for 1,7-bis(3-hydroxy-4-methoxyphenyl)-4-cyclopropylmethyl-1,6-heptadien-3,5-dione are as follows:

[0080] 1 H NMR (400 MHz, DMSO) δ 9.14 (d, J = 11.3 Hz, 2H), 7.48 (dd, J = 15.7,7.0 Hz, 2H), 7.19 – 6.94 (m, 5H), 6.88 (dd,J = 8.3, 4.3 Hz, 2H), 6.71 (d, J =15.9 Hz, 1H), 4.56 (t, J = 7.0 Hz, 1H), 3.73 (d, J = 6.0 Hz, 6H), 2.58 (d, J = 5.9Hz, 1H), 1.65 (t, J = 7.0 Hz, 1H), 0.67 (d, J = 76.2 Hz, 1H), 0.30 (ddd, J = 21.9,8.0, 1.8 Hz, 2H), 0.06 (ddd, J = 53.1, 5.0, 1.6 Hz, 2H).

[0081] 13 C NMR (101 MHz, DMSO) δ 195.83, 183.50, 150.91, 150.50, 147.22,147.19, 144.15, 141.78, 128.47, 127.45, 123.56, 122.49, 118.95, 114.70,114.53, 112.45, 62.34, 56.12, 56.09, 49.06, 33.75, 13.40, 9.66, 5.25, 4.49.

[0082] HRMS: m / z of [M+H] + Calculated for C 25 H 26 O6423.1808, found 423.1809.

[0083] Example 3

[0084] The preparation of the compound shown in formula (III) is carried out by the following reaction:

[0085] ;

[0086] The preparation steps are as follows:

[0087] (1) Same as Example 1.

[0088] (2) Dissolve 3 g of 3-cyclopropylmethyl-2,4-pentanedione and 0.7 g of boric acid in 15 mL of N,N-dimethylformamide and heat to 80 °C and reflux for 20 minutes; add 9 g of tributyl borate and 7.2 g of 3-trifluoromethoxybenzaldehyde, then add 0.7 g of n-butylamine (dissolved in 5 mL of N,N-dimethylformamide), and continue stirring at 80 °C for 2 hours; add 100 mL of 20% acetic acid aqueous solution and continue the reaction for 2 hours, precipitating a solid; cool the reaction solution to room temperature, filter, and recrystallize with methanol to obtain pure 1,7-bis(3-trifluoromethoxyphenyl)-4-n-butyl-1,6-heptadien-3,5-dione with a yield of 45%.

[0089] like Figure 9-11 The characterization data for 1,7-bis(3-trifluoromethoxyphenyl)-4-n-butyl-1,6-heptadien-3,5-dione are shown below:

[0090] 1 H NMR (400 MHz, DMSO) δ 7.88 – 7.76 (m, 4H), 7.74 (s, 1H), 7.70 (s,1H), 7.62 – 7.52 (m, 2H), 7.48 – 7.38 (m, 3H), 7.22 (d, J = 16.1 Hz, 1H), 1.89(hept, J = 7.2 Hz, 2H), 1.40 (q, J = 5.1 Hz, 2H), 1.34 – 1.19 (m, 2H), 0.88 (dt, J = 21.3, 6.9 Hz, 3H).

[0091] 13C NMR (101 MHz, DMSO) δ 196.03, 183.12, 174.23, 149.34, 141.89,140.00, 137.94, 137.16, 131.40, 131.30, 128.27, 128.10, 127.84, 123.38,123.31, 122.71, 121.82, 121.77, 121.27, 121.20, 119.22, 113.66, 62.26, 48.93,40.58, 40.37, 40.16, 39.95, 39.74, 39.54, 39.33, 35.02, 30.55, 29.78, 29.43, 28.06, 22.63, 21.79, 17.67, 14.30, 14.22.

[0092] HRMS: m / z of [M+H] + Calculated for C 25 H 22 F6O4501.1501, found 501.1501.

[0093] Experimental Case 1: Construction and Treatment of Renal Fibrosis Model

[0094] Model establishment: Male C57BL / 6J mice were anesthetized by intraperitoneal injection of 60 mg / kg pentobarbital, then shaved and prepared. A 1 cm transverse incision was made in the left abdomen of the mice, and the renal pedicle was exposed by dissection layer by layer. The left renal artery was exposed using blunt dissection, and the renal pedicle was clamped. When clamped, the left kidney turned dark brown. The clamp was released after 28 minutes. Postoperatively, the peritoneum and muscle layers were sutured layer by layer, and the skin wound was finally clamped. During the operation, the body temperature was maintained between 36 °C and 37.2 °C using a ThermoStar thermometer.

[0095] In the normal group of mice, only the skin was cut open, without clamping the kidney pedicle; all other procedures were the same as in the model group.

[0096] like Figure 1 As shown, from postoperative days 3 to 20, each treatment group received daily intraperitoneal injections of compounds (I), (II), (III), or curcumin (10 mg / kg), while the model control group and the normal control group received saline injections. On postoperative day 20, the right normal kidney was removed from anesthetized mice; on postoperative day 21 (one day after right kidney removal), the mice were sacrificed and blood and tissues were collected; serum creatinine and blood urea nitrogen levels were measured using a biochemical analyzer, and the results are shown in Tables 1 and 2, respectively; the left kidney was coronally removed, and some tissues were used for pathological examination, and the Masson staining results are shown in Tables 1 and 2, respectively; Figure 2 As shown in the figure, the kidney slices of the model group mice show obvious renal atrophy and fibrosis, indicating that the modeling was successful.

[0097] Table 1: Serum creatinine levels (mg / dL)

[0098]

[0099] Table 2: Blood urea nitrogen levels (mg / dL)

[0100]

[0101] As shown in Tables 1 and 2, 21 days post-surgery, the serum creatinine and blood urea nitrogen levels in the model group mice were significantly higher than those in the normal group. Compared to mice without intervention, curcumin administration significantly reduced serum creatinine and blood urea nitrogen levels, alleviating renal atrophy and fibrosis to some extent, but the effect was not ideal; compounds (I) and (III) showed significantly better reductions in serum creatinine and blood urea nitrogen than curcumin. Figure 2 It can be seen that compounds (I) and (III) have better inhibitory effects on renal atrophy and renal fibrosis than curcumin; compound (II) has the best effect on reducing serum creatinine and blood urea nitrogen levels, combined with Figure 2 It is known that compound (II) has the best effect in alleviating renal atrophy and renal fibrosis.

[0102] In summary, the curcumin analogues provided by this invention, such as 1,7-bis(3-hydroxy-4-methoxyphenyl)-4-n-butyl-1,6-heptadien-3,5-dione, 1,7-bis(3-hydroxy-4-methoxyphenyl)-4-cyclopropylmethyl-1,6-heptadien-3,5-dione, and 1,7-bis(3-trifluoromethoxyphenyl)-4-n-butyl-1,6-heptadien-3,5-dione, can effectively inhibit renal fibrosis, and their therapeutic effects are significantly better than those of curcumin. They have potential application value in the field of drugs for the treatment of renal fibrosis.

[0103] The above detailed embodiments describe the implementation of the present invention; however, the present invention is not limited to the specific details described in the above embodiments. Within the scope of the claims and technical concept of the present invention, various simple modifications and changes can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

Claims

1. A curcumin analogue, characterized in that, The structural formula of the curcumin analogue is as follows: ； In the formula, R1 is propyl, isopropyl, n-butyl, cyclopropylmethyl or isopentyl; R2 is 3-hydroxy and 4-methoxy, or 3-trifluoromethoxy.

2. The curcumin analogue according to claim 1, characterized in that, The structural formulas of the curcumin analogues are shown in formulas (I), (II), or (III): ； ； 。 3. The method for preparing the curcumin analogue according to any one of claims 1-2, characterized in that, The reaction formula is as follows: ； In the formula, R1 is propyl, isopropyl, n-butyl, cyclopropylmethyl or isopentyl; R2 is 3-hydroxy and 4-methoxy, or 3-trifluoromethoxy; X is chlorine, bromine or iodine; The steps are as follows: 2,4-pentanedione was subjected to a substitution reaction with a haloalkane under basic conditions to give 3-alkyl-2,4-pentanedione; 3-alkyl-2,4-pentanedione and substituted benzaldehyde undergo an aldol condensation reaction under the conditions of boric acid, tributyl borate, and n-butylamine to obtain curcumin analogues.

4. The method for preparing curcumin analogues according to claim 3, characterized in that, The temperature for the substitution reaction is 60-90 °C.

5. The method for preparing curcumin analogues according to claim 3, characterized in that, The aldol condensation reaction is carried out at a temperature of 60-90 °C.

6. The method for preparing curcumin analogues according to claim 5, characterized in that, The specific operation of the aldol condensation reaction is as follows: 3-alkyl-2,4-pentanedione and boric acid are dissolved in a solvent, heated to 60-90 ℃ and reacted for 10-30 minutes. Then, tributyl borate, substituted benzaldehyde and n-butylamine are added. After reacting for 1-3 hours, an aqueous acetic acid solution is added and the reaction is continued for 1-3 hours. A solid is precipitated, cooled to room temperature, filtered, and recrystallized from methanol to obtain curcumin analogues.

7. The use of the curcumin analogue according to any one of claims 1-2 or the curcumin analogue prepared by the preparation method according to any one of claims 4-6 in the preparation of a medicament for treating renal fibrosis.

8. A pharmaceutical composition for treating renal fibrosis, characterized in that, The pharmaceutical composition comprises the curcumin analogue according to any one of claims 1-2 or the curcumin analogue prepared by the preparation method according to any one of claims 4-6.

9. A pharmaceutical composition for treating renal fibrosis according to claim 8, characterized in that, The pharmaceutical composition further includes one or more pharmaceutically acceptable carriers or excipients.

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