CN111153912A - Curcumol derivative containing triazole structure and application thereof in preparation of medicine for treating human colorectal cancer - Google Patents
Curcumol derivative containing triazole structure and application thereof in preparation of medicine for treating human colorectal cancer Download PDFInfo
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Abstract
The invention discloses an aryl triazole curcumenol derivative shown as a formula (I) and application thereof in preparing a medicament for treating human colorectal cancer. According to the invention, a plurality of curcumenol derivatives containing triazole structures are obtained by modifying a 12-site double bond structure of curcumenol, and in-vitro cell experiments show that the curcumenol derivatives containing triazole structures show good biological activity to a human colon cancer cell Sw620 cell line, and can be used for a curcumenol derivative containing triazole structures and application thereof in preparation of medicaments for treating human colorectal cancer. Preventing or/and treating human colorectal cancer, and has great application prospect in the field of medicine. The synthesis method of the curcumenol derivative containing the triazole structure disclosed by the invention is simple and convenient, mild in reaction condition and easy to operate, and the synthesis method isIn the process, the raw materials are easy to obtain, the production cost is low, and the method is suitable for industrial production and application.
Description
Technical Field
The invention belongs to the field of natural medicines and medicinal chemistry, and particularly relates to a curcumenol derivative containing an aryl triazole structure and application thereof, in particular to a curcumenol derivative containing a triazole structure and application thereof in preparation of a medicine for treating human colorectal cancer.
Background
Colorectal cancer (carcinoma of colon and recatum) is a common malignancy in the gastrointestinal tract, second only to gastric, esophageal and primary liver cancers in digestive malignancies. Along with the improvement of the urban modernization degree, the improvement of the living standard of people, the change of the living style and the dietary structure, the increase of the high-calorie, high-fat and high-protein food intake of chicken, duck, fish and meat and the aging process of population, the problem of high colorectal tumor incidence becomes more and more prominent, and the method is worthy of attracting attention.
The traditional Chinese medicine has rich traditional Chinese medicine resources, in recent years, researchers carry out a large amount of screening on traditional Chinese medicines with tumor activity, and the traditional Chinese medicines have various action mechanisms of regulating the immunity of an organism, inhibiting tumor microangiogenesis, directly killing tumor cells, inducing tumor cell apoptosis, inducing tumor cell differentiation, reversing multiple drug resistance of cancer cells, regulating cell signal conduction, inhibiting telomerase activity and the like, and the traditional Chinese medicines have the characteristics that western medicines such as multiple target spots, multiple links and the like are difficult to have, have wide pharmacological effects, are often integrally regulated, improve the disease resistance of the organism, and achieve the anti-tumor effect through various mechanisms. With the continuous and deep experiment and clinical research on the anti-tumor effect of traditional Chinese medicines, the anti-tumor effect of traditional Chinese medicines is more and more accepted by the international society.
Curcumenol (Curcumol) is an important component of traditional Chinese medicine zedoary volatile oil, and is separated from various plants, and the plants are mostly distributed in southeast Asia, China, Indonesian, India, Peru and the like. Curcumenol (curcumenol), which is called curcumenol and curcumenol, structurally belongs to a guaiane sesquiterpenoids natural product, and is formed by fusing five-membered rings and seven-membered rings, wherein the seven-membered rings form a new five-membered ring and a new six-membered ring through an oxygen bridge of a hemiketal, so that the tension of the three rings is reduced, and a stable compound with a certain rigid structure is formed. According to the reports of documents, the curcumenol has wide biological activities of resisting virus, inflammation, tumor, early pregnancy and the like, and particularly shows potential anticancer activity in the aspect of resisting tumor, such as lung cancer, breast cancer, nasopharyngeal carcinoma, liver cancer, colorectal cancer, ovarian cancer and the like. (see literature Wei W, AzharRasul A S, Sarfraz I, et al. Curcumol: From Plant Roots to Cancer Roots [ J ]. International journal of biological sciences, 2019,15(8):1600.)
However, due to the unique chemical structure of the curcumenol, the water solubility is low, the anti-tumor activity is not outstanding, and a great optimization and improvement space exists.
Disclosure of Invention
The invention aims to provide application of a curcumenol derivative containing a triazole structure in preparation of a drug for treating colorectal cancer, and the curcumenol derivative containing the triazole structure has a good inhibition effect on a human colorectal cancer cell line Sw620 cell line under an effective dose.
The technical scheme adopted by the invention is as follows:
a curcumenol derivative containing triazole structure has the following structure as shown in formula (I):
in the formula (I), R is halogen or C1-C6Alkyl radical, C1-C6Alkoxy radical, C1-C6Sulfonyl radical, C1-C6Alkylthio, fluoroalkyl substituted aryl or substituted heteroaryl.
Further, preferably, R is a halogen atom or a C atom1-C6Alkyl radical, C1-C6Alkoxy radical, C1-C6Sulfonyl radical, C1-C6Alkylthio, fluoroalkyl substituted phenyl.
Still further, preferably, R is phenyl, 4-nitrophenyl, 4-chlorophenyl, 4-methoxyphenyl, 4-methylphenyl, 2-fluorophenyl, 3-chlorophenyl, 2-methoxy-4-fluorophenyl, 2, 4-difluorophenyl or 2-bromophenyl.
Furthermore, the structure of the curcumenol derivative containing the triazole structure is preferably any one of compounds shown as formulas C-01-C-10:
the invention also provides a curcumenol derivative containing a triazole structure, which is applied to the preparation of anti-tumor cell drugs.
Furthermore, the tumor cell is a human colorectal cancer cell.
Still further, said human colorectal cancer cell is preferably a Sw620 cancer cell.
On the other hand, the invention also provides a medicament for treating human colorectal cancer, which comprises an effective dose of curcumenol derivatives containing triazole structures.
In addition, the invention also provides a synthesis method of the curcumenol derivative containing the triazole structure shown in the formula I, and the specific synthetic route is as follows:
the synthesis method comprises the following steps:
(1) dissolving a natural product of a curcuma alcohol in an organic solvent A, adding m-chloroperoxybenzoic acid (m-CPBA) in batches at the temperature of-5-0 ℃, reacting for 1-6 h at the temperature of 0-50 ℃ after 30min, detecting by TLC, adding water into the obtained reaction liquid A after the reaction is finished, extracting by ethyl acetate, combining organic phases, washing the organic phases by a saturated sodium chloride solution, concentrating, separating and purifying by column chromatography to obtain a compound shown in a formula (II); the ratio of the amount of the curcumenol compound to the amount of the m-CPBA feeding substance is 1: 2-5;
(2) dissolving a compound shown as a formula (II) in an organic solvent B, stirring for reaction at 30-100 ℃, stirring for 10min, adding an alkaline substance A, reacting for 1-10 h at 30-100 ℃, detecting by TLC, reacting to obtain a reaction solution B, cooling to room temperature, pouring the reaction solution into ice water, standing for 1-3 h, precipitating a white solid, and filtering to obtain a compound shown as a formula (III); the amount ratio of the compound shown in the formula (II) to the basic substance A is 1: 0.2-1;
(3) dissolving a compound shown as a formula (III) in an organic solvent C, adding an alkaline substance C, stirring at 0-30 ℃ for reaction for 15min, dropwise adding a compound 3-bromopropyne, reacting at 0-30 ℃ for 10-24 h, detecting by TLC (thin layer chromatography), after the reaction is finished, adding water and ethyl acetate into the obtained reaction solution C, extracting, combining organic phases, washing the organic phase with a saturated sodium chloride solution, concentrating, and carrying out column chromatography separation and purification to obtain a compound shown as a formula (IV); the ratio of the amount of the compound of formula (III), the basic substance C and the 3-bromopropyne is 1: 1-5: 1 to 1.5;
(4) dissolving a compound shown as a formula (IV) in an organic solvent D, sequentially adding copper sulfate pentahydrate, ascorbic acid and substituted aryl azide shown as a formula (V), reacting at 0-30 ℃ for 4-8 h, detecting by TLC (thin layer chromatography), after the reaction is finished, adding water and ethyl acetate into the obtained reaction solution D, extracting, combining organic phases, washing the organic phase with a saturated sodium chloride solution, concentrating, and carrying out column chromatography separation and purification to obtain a compound shown as a formula (I); the ratio of the amount of the compound shown in the formula (IV), copper sulfate pentahydrate, ascorbic acid and the amount of the substituted aryl azide shown in the formula (V) is 1: 0.2: 0.1-0.5: 1-1.5.
Further, in the step (1):
the organic solvent A is selected from one of the following: tetrahydrofuran, dichloromethane, chloroform, 1, 2-dichloroethane, toluene, acetonitrile or 1, 4-dioxane, preferably tetrahydrofuran or dichloromethane; the dosage of the organic solvent A is 10-50 mL/g calculated by the mass of the curcumenol compound.
Preferably, the reaction temperature is-5-0 ℃, and the reaction time is 1-3 h.
The ratio of the amount of the curcumenol compound to the amount of the m-CPBA is preferably 1:2 to 3.
Further, in the step (2):
the organic solvent B is toluene, tetrahydrofuran, ethanol, methanol or 1, 4-dioxane. Preferably ethanol or methanol; the dosage of the organic solvent B is 10-50 mL/g based on the mass shown in the formula (II).
The alkaline substance A is sodium hydride, sodium methoxide, sodium ethoxide, pyridine, potassium tert-butoxide, sodium hydroxide or potassium hydroxide, preferably sodium hydroxide or potassium hydroxide.
Preferably, the reaction temperature is 70-80 ℃, and the reaction time is 5-8 h.
The ratio of the amounts of the feed materials of the formula (II) and the alkaline material A is preferably 1: 0.5 to 0.8.
Further, in the step (3):
the organic solvent C is selected from one of the following: tetrahydrofuran, dichloromethane, chloroform, 1, 2-dichloroethane, toluene, acetonitrile or 1, 4-dioxane, preferably tetrahydrofuran or toluene; the dosage of the organic solvent C is 10-50 mL/g based on the mass of the compound shown in the formula (III).
Preferably, the reaction temperature is 10-25 ℃, and the reaction time is 10-20 h.
The alkaline substance B is selected from sodium carbonate, sodium bicarbonate, potassium carbonate, cesium carbonate, sodium phosphate, sodium hydroxide or potassium hydroxide, and preferably sodium hydroxide or potassium hydroxide.
The ratio of the amount of the compound of the formula (III), the basic substance C and the feeding substance of 3-bromopropyne is 1: 1-5: 1 to 1.5, preferably 1: 1.6: 1.1 to 1.3.
In the step (4):
the organic solvent D is selected from one of the following: tetrahydrofuran, dichloromethane, chloroform, 1, 2-dichloroethane, toluene, ethyl acetate, acetonitrile or 1, 4-dioxane, preferably tetrahydrofuran or ethyl acetate; the amount of the organic solvent D is 10-50 mL/g based on the mass of the compound shown in the formula (IV).
Preferably, the reaction temperature is 10-25 ℃, and the reaction time is 4-6 h.
The ratio of the amounts of the compound shown in the formula (IV), copper sulfate pentahydrate, ascorbic acid and the substituted aryl azide shown in the formula (V) is preferably 1: 0.2: 0.1 to 0.3: 1 to 1.2.
Compared with the prior art, the invention has the following beneficial effects:
(1) according to the invention, a plurality of curcumenol derivatives containing triazole structures are obtained by modifying a 12-site double bond structure of curcumenol, and in-vitro cell experiments show that the curcumenol derivatives containing triazole structures show good biological activity on a human colon cancer cell Sw620 cell line, can be used for preventing or/and treating human colorectal cancer, and has a huge application prospect in the field of medicines.
(2) The synthesis method of the curcumenol derivative containing the triazole structure disclosed by the invention is simple and convenient, mild in reaction condition, easy to operate, easy in raw material obtaining and low in production cost in the synthesis process, and is suitable for industrial production and application.
Drawings
FIG. 1 is a nuclear magnetic spectrum of compound C-02 obtained in example 2;
FIG. 2 is a nuclear magnetic spectrum of Compound C-08 obtained in example 8;
FIG. 3 is a nuclear magnetic spectrum of Compound C-09 obtained in example 9.
Detailed description of the invention
The examples and preparations provided below further illustrate and exemplify the present compounds, and it should be understood that the scope of the following examples and preparations is not intended to limit the scope of the present invention in any way.
Example 1: synthesis of curcumenol derivative C-01 containing aryl triazole structure
Dissolving 5.0g (21.15mmol) of curcumenol in 50mL of dichloromethane, adding 7.30g (42.31mmol) of m-CPBA (m-chloroperoxybenzoic acid) in batches under the condition of ice-water bath, transferring to room temperature and 25 ℃ after 30min of dropwise addition is finished, stirring for 3h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding saturated sodium bicarbonate to remove residual m-chloroperoxybenzoic acid, extracting with ethyl acetate, combining ethyl acetate phases, washing an ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a compound 1-1(4.87g) which is a light yellow oily product with the yield of 91.22%.
Dissolving 1-12.0 g (7.93mmol) of compound in 20mL of ethanol, heating to 70 ℃, stirring, adding 0.17g (4.25mmol) of sodium hydroxide, heating and refluxing for 2h, naturally cooling to room temperature, detecting by TLC until the reaction is complete, adding into 100mL of ice water, standing to precipitate white solid, and obtaining the compound 1-2(1.21g) with the yield of 60%.1H NMR(500MHz, CD3OD)δ5.80(d,J＝1.2Hz,1H),4.01(d,J＝1.4Hz,2H),2.21(dd,J ＝12.6,10.9Hz,1H),2.10(t,J＝8.7Hz,1H),1.96(m,3H),1.87(m,1H), 1.62(m,3H),1.56(dd,J＝12.7,7.4Hz,1H),1.01(d,J＝6.5Hz,3H), 1.29(d,J＝6.5Hz,3H),0.91(d,J＝6.6Hz,3H).
Dissolving 1-21.0 g (3.96mmol) of compound in 20ml tetrahydrofuran, adding 0.36g (1.60mmol) of potassium hydroxide, stirring at room temperature of 25 ℃ for reaction for 15min, dropwise adding 0.52g (4.36mmol) of compound 3-bromopropyne, reacting at room temperature of 25 ℃ for 12h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 3:1 gave compound 1-3(0.65g) as a pale yellow oil, 56.48% yield.
Dissolving 1-30.5 g (1.72mmol) of the compound in 10ml of ethyl acetate, sequentially adding 100mg of copper sulfate pentahydrate, 80mg of ascorbic acid and 0.225g (1.89mmol) of azidobenzene, stirring at room temperature and 25 ℃ for reaction for 4h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, separating and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 5:1Compound C-01(0.4g) was obtained as a pale yellow oily product in 56.73% yield.1H NMR(500MHz,Chloroform-d)δ 8.01(s,1H),7.75–7.66(m,2H),7.54–7.46(m,2H),7.42–7.43(m,1H),5.89(d,J＝1.6Hz,1H),4.90(q,J＝12.8Hz,1H),4.76–4.58(m,1H), 4.16–3.93(m,2H),3.92–3.71(m,1H),2.93(d,J＝1.3Hz,1H),2.86(d, J＝1.3Hz,1H),2.24–2.12(m,1H),2.10–1.96(m,1H),1.95–1.76(m, 4H),1.68(m,1H),1.51–1.53(m,3H),1.30–1.19(m,2H),0.99(d,J＝6.6 Hz,7H),0.97(d,J＝6.6Hz,7H),0.85(d,J＝6.6Hz,3H).
Example 2: synthesis of curcumenol derivative C-02 containing aryl triazole structure
Dissolving 5.0g (21.15mmol) of curcumenol in 50mL of dichloromethane, adding 7.30g (42.31mmol) of m-CPBA (m-chloroperoxybenzoic acid) in batches under the condition of ice-water bath, transferring to room temperature and 25 ℃ after 30min of dropwise addition is finished, stirring for 3h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding saturated sodium bicarbonate to remove residual m-chloroperoxybenzoic acid, extracting with ethyl acetate, combining ethyl acetate phases, washing an ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a compound 1-1(4.87g) which is a light yellow oily product with the yield of 91.22%.
Dissolving 1-12.0 g (7.93mmol) of compound in 20mL of ethanol, heating to 70 ℃, stirring, adding 0.17g (4.25mmol) of sodium hydroxide, heating and refluxing for 2h, naturally cooling to room temperature, detecting by TLC until the reaction is complete, adding into 100mL of ice water, standing to precipitate white solid, and obtaining the compound 1-2(1.21g) with the yield of 60%.
Dissolving 1-21.0 g (3.96mmol) of compound in 20ml tetrahydrofuran, adding 0.36g (1.60mmol) of potassium hydroxide, stirring at room temperature of 25 ℃ for reaction for 15min, dropwise adding 0.52g (4.36mmol) of compound 3-bromopropyne, reacting at room temperature of 25 ℃ for 12h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 3:1 gave compound 1-3(0.65g) as a pale yellow oil, 56.48% yield.
Dissolving 1-30.5 g (1.72mmol) of the compound in 10ml of ethyl acetate, sequentially adding 100mg of copper sulfate pentahydrate, 80mg of ascorbic acid and 0.225g (1.89mmol) of p-nitroazide, stirring at room temperature and 25 ℃ for reaction for 4h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, separating and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 5:1 gave compound C-02(0.45g) as a pale yellow oil in 57.50% yield.1H NMR(500MHz,Chloroform-d) δ8.40(d,J＝9.1Hz,2H),8.15(s,1H),7.96(d,J＝9.1Hz,2H),5.92(d, J＝1.6Hz,1H),5.02–4.83(m,2H),4.18–4.04(m,2H),2.20(dd,J＝ 12.7,10.9Hz,1H),2.06–1.99(m,1H),1.96–1.82(m,4H),1.57–1.45 (m,3H),1.31–1.21(m,3H),1.00(d,J＝6.5Hz,3H),0.95(d,J＝6.5Hz, 3H),0.86(d,J＝6.6Hz,3H).
Example 3: synthesis of curcumenol derivative C-03 containing aryl triazole structure
Dissolving 5.0g (21.15mmol) of curcumenol in 50mL of dichloromethane, adding 7.30g (42.31mmol) of m-CPBA (m-chloroperoxybenzoic acid) in batches under the condition of ice-water bath, transferring to room temperature and 25 ℃ after 30min of dropwise addition is finished, stirring for 3h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding saturated sodium bicarbonate to remove residual m-chloroperoxybenzoic acid, extracting with ethyl acetate, combining ethyl acetate phases, washing an ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a compound 1-1(4.87g) which is a light yellow oily product with the yield of 91.22%.
Dissolving 1-12.0 g (7.93mmol) of compound in 20mL of ethanol, heating to 70 ℃, stirring, adding 0.17g (4.25mmol) of sodium hydroxide, heating and refluxing for 2h, naturally cooling to room temperature, detecting by TLC until the reaction is complete, adding into 100mL of ice water, standing to precipitate white solid, and obtaining the compound 1-2(1.21g) with the yield of 60%.
Dissolving 1-21.0 g (3.96mmol) of compound in 20ml tetrahydrofuran, adding 0.36g (1.60mmol) of potassium hydroxide, stirring at room temperature of 25 ℃ for reaction for 15min, dropwise adding 0.52g (4.36mmol) of compound 3-bromopropyne, reacting at room temperature of 25 ℃ for 12h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 3:1 gave compound 1-3(0.65g) as a pale yellow oil, 56.48% yield.
Dissolving 1-30.5 g (1.72mmol) of the compound in 10ml of ethyl acetate, sequentially adding 100mg of copper sulfate pentahydrate, 80mg of ascorbic acid and 0.29g (1.89mmol) of p-chloro-azidobenzene, stirring at room temperature and 25 ℃ for reaction for 4h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, separating and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 5:1 gave compound C-03(0.52g) as a pale yellow oil in 68.29% yield.1H NMR(500MHz,Chloroform-d) δ7.98(s,1H),7.67(dd,J＝11.9,8.8Hz,2H),7.48(dd,J＝8.9,6.9Hz, 2H),5.91(dd,J＝6.6,1.4Hz,1H),4.90(q,J＝12.8Hz,1H),4.76–4.58 (m,1H),4.13–4.06(m,2H),3.98(dd,J＝12.9,1.2Hz,1H),2.20(td,J＝12.6,10.8Hz,1H),2.10–1.98(m,1H),1.88(m,4H),1.69(td,J＝10.8, 7.3Hz,1H),1.60–1.43(m,3H),1.30–1.19(m,2H),1.04–0.91(m,6H), 0.86(dd,J＝8.8,6.5Hz,3H).
Example 4: synthesis of curcumenol derivative C-04 containing aryl triazole structure
Dissolving 5.0g (21.15mmol) of curcumenol in 50mL of dichloromethane, adding 7.30g (42.31mmol) of m-CPBA (m-chloroperoxybenzoic acid) in batches under the condition of ice-water bath, transferring to room temperature and 25 ℃ after 30min of dropwise addition is finished, stirring for 3h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding saturated sodium bicarbonate to remove residual m-chloroperoxybenzoic acid, extracting with ethyl acetate, combining ethyl acetate phases, washing an ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a compound 1-1(4.87g) which is a light yellow oily product with the yield of 91.22%.
Dissolving 1-12.0 g (7.93mmol) of compound in 20mL of ethanol, heating to 70 ℃, stirring, adding 0.17g (4.25mmol) of sodium hydroxide, heating and refluxing for 2h, naturally cooling to room temperature, detecting by TLC until the reaction is complete, adding into 100mL of ice water, standing to precipitate white solid, and obtaining the compound 1-2(1.21g) with the yield of 60%.
Dissolving 1-21.0 g (3.96mmol) of compound in 20ml tetrahydrofuran, adding 0.36g (1.60mmol) of potassium hydroxide, stirring at room temperature of 25 ℃ for reaction for 15min, dropwise adding 0.52g (4.36mmol) of compound 3-bromopropyne, reacting at room temperature of 25 ℃ for 12h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 3:1 gave compound 1-3(0.65g) as a pale yellow oil, 56.48% yield.
Dissolving 1-30.5 g (1.72mmol) of the compound in 10ml of ethyl acetate, sequentially adding 100mg of copper sulfate pentahydrate, 80mg of ascorbic acid and 0.28g (1.89mmol) of p-methoxyazidobenzene, stirring at room temperature and 25 ℃ for reaction for 4h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, separating and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 5:1 gave compound C-04(0.56g) as a pale yellow solidThe product was obtained as a yellow oil in 74% yield.1H NMR(500MHz,Chloroform-d)δ 7.90(s,1H),7.62–7.52(m,2H),6.96(m,2H),5.90(d,J＝1.4Hz,1H), 4.86(q,J＝12.8Hz,2H),4.16–4.03(m,2H),3.81(s,3H),2.14(dd,J＝ 12.7,11.0Hz,1H),2.05–1.95(m,1H),1.93–1.75(m,4H),1.57–1.41(m, 3H),1.27–1.18(m,1H),0.94(dd,J＝31.2,6.5Hz,6H),0.81(d,J＝6.6 Hz,3H).
Example 5: synthesis of curcumenol derivative C-05 containing aryl triazole structure
Dissolving 5.0g (21.15mmol) of curcumenol in 50mL of dichloromethane, adding 7.30g (42.31mmol) of m-CPBA (m-chloroperoxybenzoic acid) in batches under the condition of ice-water bath, transferring to room temperature and 25 ℃ after 30min of dropwise addition is finished, stirring for 3h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding saturated sodium bicarbonate to remove residual m-chloroperoxybenzoic acid, extracting with ethyl acetate, combining ethyl acetate phases, washing an ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a compound 1-1(4.87g) which is a light yellow oily product with the yield of 91.22%.
Dissolving 1-12.0 g (7.93mmol) of compound in 20mL of ethanol, heating to 70 ℃, stirring, adding 0.17g (4.25mmol) of sodium hydroxide, heating and refluxing for 2h, naturally cooling to room temperature, detecting by TLC until the reaction is complete, adding into 100mL of ice water, standing to precipitate white solid, and obtaining the compound 1-2(1.21g) with the yield of 60%.
Dissolving 1-21.0 g (3.96mmol) of compound in 20ml tetrahydrofuran, adding 0.36g (1.60mmol) of potassium hydroxide, stirring at room temperature of 25 ℃ for reaction for 15min, dropwise adding 0.52g (4.36mmol) of compound 3-bromopropyne, reacting at room temperature of 25 ℃ for 12h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 3:1 gave compound 1-3(0.65g) as a pale yellow oil, 56.48% yield.
Dissolving 1-30.5 g (1.72mmol) of the compound in 10ml of ethyl acetate, sequentially adding 100mg of copper sulfate pentahydrate, 80mg of ascorbic acid and 0.259g (1.89mmol) of o-fluoro azidobenzene, stirring at room temperature and 25 ℃ for reaction for 4 hours, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, separating and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 5:1 gave compound C-05(0.56g) as a pale yellow oil in 74% yield.1H NMR(500MHz,Chloroform-d)δ 8.02(s,1H),7.81(m,1H),7.32(m,1H),7.25–7.14(m,2H),5.84(d,J＝ 1.5Hz,1H),4.92–4.75(m,1H),4.07–3.98(m,2H),2.09(td,J＝12.5, 10.8Hz,1H),2.02–1.91(m,1H),1.79(qdd,J＝14.8,13.5,7.3,4.3Hz, 4H),1.44(m,3H),1.17(dd,J＝12.7,7.4Hz,1H),0.95–0.83(m,6H), 0.75(d,J＝6.5Hz,3H).
Example 6: synthesis of curcumenol derivative C-06 containing aryl triazole structure
Dissolving 5.0g (21.15mmol) of curcumenol in 50mL of dichloromethane, adding 7.30g (42.31mmol) of m-CPBA (m-chloroperoxybenzoic acid) in batches under the condition of ice-water bath, transferring to room temperature and 25 ℃ after 30min of dropwise addition is finished, stirring for 3h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding saturated sodium bicarbonate to remove residual m-chloroperoxybenzoic acid, extracting with ethyl acetate, combining ethyl acetate phases, washing an ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a compound 1-1(4.87g) which is a light yellow oily product with the yield of 91.22%.
Dissolving 1-12.0 g (7.93mmol) of compound in 20mL of ethanol, heating to 70 ℃, stirring, adding 0.17g (4.25mmol) of sodium hydroxide, heating and refluxing for 2h, naturally cooling to room temperature, detecting by TLC until the reaction is complete, adding into 100mL of ice water, standing to precipitate white solid, and obtaining the compound 1-2(1.21g) with the yield of 60%.
Dissolving 1-21.0 g (3.96mmol) of compound in 20ml tetrahydrofuran, adding 0.36g (1.60mmol) of potassium hydroxide, stirring at room temperature of 25 ℃ for reaction for 15min, dropwise adding 0.52g (4.36mmol) of compound 3-bromopropyne, reacting at room temperature of 25 ℃ for 12h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 3:1 gave compound 1-3(0.65g) as a pale yellow oil, 56.48% yield.
Dissolving 1-30.5 g (1.72mmol) of the compound in 10ml of ethyl acetate, sequentially adding 100mg of copper sulfate pentahydrate, 80mg of ascorbic acid and 0.25g (1.89mmol) of p-methyl azidobenzene, stirring at room temperature and 25 ℃ for reaction for 4h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, separating and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 5:1 gave compound C-06(0.56g) as a pale yellow oil in 76.79% yield.1H NMR(500MHz,Chloroform-d) δ7.97(s,1H),7.57(d,J＝8.4Hz,2H),7.26(d,J＝8.2Hz,2H),5.86(d, J＝1.5Hz,1H),4.73–4.56(m,2H),4.16–4.01(m,2H),2.37(s,3H),2.17 (dd,J＝12.9,10.9Hz,1H),2.04(t,J＝8.7Hz,1H),1.83(m,3H),1.68 (m,1H),1.59–1.42(m,3H),1.23(dd,J＝12.7,7.5Hz,1H),0.98(dd,J＝ 6.5,2.2Hz,6H),0.84(d,J＝6.6Hz,3H).
Example 7: synthesis of curcumenol derivative C-07 containing aryl triazole structure
Dissolving 5.0g (21.15mmol) of curcumenol in 50mL of dichloromethane, adding 7.30g (42.31mmol) of m-CPBA (m-chloroperoxybenzoic acid) in batches under the condition of ice-water bath, transferring to room temperature and 25 ℃ after 30min of dropwise addition is finished, stirring for 3h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding saturated sodium bicarbonate to remove residual m-chloroperoxybenzoic acid, extracting with ethyl acetate, combining ethyl acetate phases, washing an ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a compound 1-1(4.87g) which is a light yellow oily product with the yield of 91.22%.
Dissolving 1-12.0 g (7.93mmol) of compound in 20mL of ethanol, heating to 70 ℃, stirring, adding 0.17g (4.25mmol) of sodium hydroxide, heating and refluxing for 2h, naturally cooling to room temperature, detecting by TLC until the reaction is complete, adding into 100mL of ice water, standing to precipitate white solid, and obtaining the compound 1-2(1.21g) with the yield of 60%.
Dissolving 1-21.0 g (3.96mmol) of compound in 20ml tetrahydrofuran, adding 0.36g (1.60mmol) of potassium hydroxide, stirring at room temperature of 25 ℃ for reaction for 15min, dropwise adding 0.52g (4.36mmol) of compound 3-bromopropyne, reacting at room temperature of 25 ℃ for 12h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 3:1 gave compound 1-3(0.65g) as a pale yellow oil, 56.48% yield.
Dissolving 1-30.5 g (1.72mmol) of the compound in 10ml of ethyl acetate, sequentially adding 100mg of copper sulfate pentahydrate, 80mg of ascorbic acid and 0.29g (1.89mmol) of m-chloro azidobenzene, stirring at room temperature and 25 ℃ for reaction for 4h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, separating and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 5:1 gave compound C-07(0.52g) as a pale yellow oil in 69.20% yield.1H NMR(500MHz,Chloroform-d) δ8.02(s,1H),7.78(t,J＝2.0Hz,1H),7.64(m,1H),7.48–7.38(m,2H), 5.88(s,1H),4.77–4.56(m,2H),4.03(m,2H),2.21(dd,J＝12.8,10.8 Hz,1H),2.06(t,J＝8.5Hz,1H),1.95–1.78(m,3H),1.68(m,1H),1.61 –1.45(m,3H),1.26(dd,J＝12.8,7.4Hz,1H),1.05–0.97(m,6H),0.87 (d,J＝6.5Hz,3H).
Example 8: synthesis of curcumenol derivative C-08 containing aryl triazole structure
Dissolving 5.0g (21.15mmol) of curcumenol in 50mL of dichloromethane, adding 7.30g (42.31mmol) of m-CPBA (m-chloroperoxybenzoic acid) in batches under the condition of ice-water bath, transferring to room temperature and 25 ℃ after 30min of dropwise addition is finished, stirring for 3h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding saturated sodium bicarbonate to remove residual m-chloroperoxybenzoic acid, extracting with ethyl acetate, combining ethyl acetate phases, washing an ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a compound 1-1(4.87g) which is a light yellow oily product with the yield of 91.22%.
Dissolving 1-12.0 g (7.93mmol) of compound in 20mL of ethanol, heating to 70 ℃, stirring, adding 0.17g (4.25mmol) of sodium hydroxide, heating and refluxing for 2h, naturally cooling to room temperature, detecting by TLC until the reaction is complete, adding into 100mL of ice water, standing to precipitate white solid, and obtaining the compound 1-2(1.21g) with the yield of 60%.
Dissolving 1-21.0 g (3.96mmol) of compound in 20ml tetrahydrofuran, adding 0.36g (1.60mmol) of potassium hydroxide, stirring at room temperature of 25 ℃ for reaction for 15min, dropwise adding 0.52g (4.36mmol) of compound 3-bromopropyne, reacting at room temperature of 25 ℃ for 12h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 3:1 gave compound 1-3(0.65g) as a pale yellow oil, 56.48% yield.
Dissolving 1-30.5 g (1.72mmol) of the compound in 10ml of ethyl acetate, and sequentially adding 100mg of copper sulfate pentahydrate and ascorbic acidAcid 80mg, 2-methoxy-4-fluoroazidobenzene 0.32g (1.89mmol), stirring at room temperature 25 ℃ for reaction for 4h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated aqueous sodium chloride solution three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, separating and purifying by column chromatography, wherein the mobile phase ratio is petroleum ether: ethyl acetate 5:1 gave compound C-08 (0.62g) as a pale yellow oil in 78.83% yield.1H NMR(500MHz, Chloroform-d)δ8.01(s,1H),7.65(m,1H),6.83–6.68(m,2H),5.87(dd, J＝13.7,1.5Hz,1H),4.94–4.81(m,1H),4.72–4.53(m,1H),4.09– 4.02(m,2H),3.84(s,3H),2.15(ddd,J＝15.1,12.6,10.8Hz,1H),2.07– 1.95(m,2H),1.84(m,4H),1.66(m,1H),1.50(m,4H),1.26–1.17(m, 2H),0.94(dd,J＝30.9,6.5Hz,6H),0.82(dd,J＝12.7,6.5Hz,3H).
Example 9: synthesis of curcumenol derivative C-09 containing aryl triazole structure
Dissolving 5.0g (21.15mmol) of curcumenol in 50mL of dichloromethane, adding 7.30g (42.31mmol) of m-CPBA (m-chloroperoxybenzoic acid) in batches under the condition of ice-water bath, transferring to room temperature and 25 ℃ after 30min of dropwise addition is finished, stirring for 3h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding saturated sodium bicarbonate to remove residual m-chloroperoxybenzoic acid, extracting with ethyl acetate, combining ethyl acetate phases, washing an ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a compound 1-1(4.87g) which is a light yellow oily product with the yield of 91.22%.
Dissolving 1-12.0 g (7.93mmol) of compound in 20mL of ethanol, heating to 70 ℃, stirring, adding 0.17g (4.25mmol) of sodium hydroxide, heating and refluxing for 2h, naturally cooling to room temperature, detecting by TLC until the reaction is complete, adding into 100mL of ice water, standing to precipitate white solid, and obtaining the compound 1-2(1.21g) with the yield of 60%.
Dissolving 1-21.0 g (3.96mmol) of compound in 20ml tetrahydrofuran, adding 0.36g (1.60mmol) of potassium hydroxide, stirring at room temperature of 25 ℃ for reaction for 15min, dropwise adding 0.52g (4.36mmol) of compound 3-bromopropyne, reacting at room temperature of 25 ℃ for 12h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 3:1 gave compound 1-3(0.65g) as a pale yellow oil, 56.48% yield.
Dissolving 1-30.5 g (1.72mmol) of the compound in 10ml of ethyl acetate, sequentially adding 100mg of copper sulfate pentahydrate, 80mg of ascorbic acid and 0.29g (1.89mmol) of 2, 4-difluoroazidobenzene, stirring and reacting for 4h at room temperature and 25 ℃, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing an ethyl acetate layer with a saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, separating and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 5:1 gave compound C-09(0.58g) as a pale yellow oil, 75.61% yield.1H NMR(500MHz,Chloroform-d) δ8.01(d,J＝2.7Hz,1H),7.91–7.79(m,1H),7.07–6.95(m,2H),5.86 (dd,J＝16.7,1.5Hz,1H),4.92–4.57(m,2H),4.18–3.99(m,2H),3.93 (dd,J＝12.8,1.1Hz,1H),2.14(ddd,J＝13.9,12.7,10.9Hz,1H),2.07– 1.95(m,1H),1.89–1.73(m,4H),1.66(td,J＝10.8,7.4Hz,1H),1.55– 1.39(m,3H),1.21(dd,J＝13.0,7.4Hz,1H),1.00–0.86(m,6H),0.81 (dd,J＝11.9,6.6Hz,3H).
Example 10: synthesis of curcumenol derivative C-10 containing aryl triazole structure
Dissolving 5.0g (21.15mmol) of curcumenol in 50mL of dichloromethane, adding 7.30g (42.31mmol) of m-CPBA (m-chloroperoxybenzoic acid) in batches under the condition of ice-water bath, transferring to room temperature and 25 ℃ after 30min of dropwise addition is finished, stirring for 3h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding saturated sodium bicarbonate to remove residual m-chloroperoxybenzoic acid, extracting with ethyl acetate, combining ethyl acetate phases, washing an ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a compound 1-1(4.87g) which is a light yellow oily product with the yield of 91.22%.
Dissolving 1-12.0 g (7.93mmol) of compound in 20mL of ethanol, heating to 70 ℃, stirring, adding 0.17g (4.25mmol) of sodium hydroxide, heating and refluxing for 2h, naturally cooling to room temperature, detecting by TLC until the reaction is complete, adding into 100mL of ice water, standing to precipitate white solid, and obtaining the compound 1-2(1.21g) with the yield of 60%.
Dissolving 1-21.0 g (3.96mmol) of compound in 20ml tetrahydrofuran, adding 0.36g (1.60mmol) of potassium hydroxide, stirring at room temperature of 25 ℃ for reaction for 15min, dropwise adding 0.52g (4.36mmol) of compound 3-bromopropyne, reacting at room temperature of 25 ℃ for 12h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 3:1 gave compound 1-3(0.65g) as a pale yellow oil, 56.48% yield.
Dissolving 1-30.5 g (1.72mmol) of the compound in 10ml of ethyl acetate, sequentially adding 100mg of copper sulfate pentahydrate, 80mg of ascorbic acid and 0.37g (1.89mmol) of o-bromoazidobenzene, stirring at room temperature and 25 ℃ for reaction for 4h, detecting the reaction by TLC until the reaction is complete, concentrating the reaction solution, adding water, extracting with ethyl acetate, combining ethyl acetate phases, washing the ethyl acetate layer with saturated sodium chloride aqueous solution for three times, drying with anhydrous sodium sulfate, concentrating under reduced pressure, separating and purifying by column chromatography, wherein the mobile phase proportion is petroleum ether: ethyl acetate 5:1 gave compound C-10(0.54g) as a pale yellow oil in 64.21% yield.1H NMR(500MHz,Chloroform-d) δ7.92(d,J＝8.0Hz,1H),7.70(dd,J＝7.9,6.1Hz,1H),7.52–7.39(m, 2H),7.39–7.30(m,1H),5.87(d,J＝14.0Hz,1H),4.95–4.54(m,2H), 4.11–4.00(m,2H),2.15(q,J＝13.2,12.6Hz,1H),2.08–1.94(m,1H), 1.91–1.72(m,4H),1.66(m,1H),1.56–1.40(m,4H),1.28–1.17(m,2H), 0.93(dd,J＝29.4,6.3Hz,6H),0.82(dd,J＝12.2,6.8Hz,3H).
Application example: in vitro antitumor assay
The curcumenol derivatives synthesized in the above examples were selected to perform in vitro anti-tumor activity experiments, 7 cell lines were screened, a549 (non-small cell lung cancer), IR (non-small cell lung cancer), PC-9 (lung cancer), KU812 (human peripheral hemophilous leukemia), DU145 (human prostate cancer), SW620 (human colon cancer) cell lines were subjected to MTT reduction to determine the inhibitory activity of curcumenol derivatives against various human cancer cell lines, and the drug concentration at which the inhibitory rate reached 50%, i.e., IC, was calculated50。
SW620 human colon cancer cells in logarithmic growth phase are selected and digested by pancreatin, and then the L-15 culture medium is prepared into 6 multiplied by 104A cell suspension of/mL, then adding the cell suspension to a 96-well plate at 15000 cells per well, 37 ℃ CO-free2Culturing for 24 hr, adding the prepared drugs with different concentrations into 96-well plate with concentration gradient of 100 μ M, 75 μ M, 50 μ M, 25 μ M, and 10 μ M, each concentration gradient having 4 auxiliary wells, and keeping temperature at 37 deg.C without CO2Culturing for 72 hr, adding 10 μ LMTT into each well, and keeping temperature at 37 deg.C without CO2Culturing for 3 hr, discarding supernatant, adding 150 μ LDMSO, oscillating, and measuring optical density (OD value) at 490nm with microplate reader
HCT116 human colon cancer cells in logarithmic growth phase are selected, digested by pancreatin, and prepared into 6 x 10 by DMEM medium4A cell suspension of/mL, then adding the cell suspension to a 96-well plate at 5000 cells per well, 5% CO at 37 ℃2Culturing for 24 hr, adding the prepared drugs with different concentrations into 96-well plate with concentration gradient of 100 μ M, 75 μ M, 50 μ M, 25 μ M, and 10 μ M, each concentration gradient having 4 auxiliary wells, and 5% CO at 37 deg.C2After 72 hours of incubation, 10. mu.L of MTT (5mg/mL) solution was added to each well at 37 ℃ in 5% CO2Culturing for 3 hours, discarding the supernatant, adding 150 μ L DMSO, oscillating, and measuring optical density (OD value) at 490nm with enzyme labeling instrument;
and (3) calculating an inhibition rate:
growth inhibition rate (OD control-OD experimental group)/(OD control-OD blank group)
Calculating IC according to the drug concentration-growth inhibition rate curve50The results are shown in table 1 below:
TABLE 1
TABLE 2
As can be seen from tables 1 and 2, the compounds provided by the invention have good colon cancer resistance, particularly, the C-05 and C-09 compounds show the biological activity on the Sw620 cell line which is equivalent to that of the antitumor drug of pentafluorouracil, and the compounds have good development prospects in the field of pharmaceutical chemistry.
Claims (8)
1. A curcumenol derivative containing triazole structure shown in the following formula (I):
in the formula (I), R is halogen or C1-C6Alkyl radical, C1-C6Alkoxy radical, C1-C6Sulfonyl radical, C1-C6Alkylthio, fluoroalkyl substituted aryl or substituted heteroaryl.
2. The curcumenol derivative with triazole structure of claim 1, wherein: r is halogen or C1-C6Alkyl radical, C1-C6Alkoxy radical, C1-C6Sulfonyl radicalBase, C1-C6Alkylthio, fluoroalkyl substituted phenyl.
3. The curcumenol derivative with triazole structure of claim 1, wherein: and R is phenyl, 4-nitrophenyl, 4-chlorphenyl, 4-methoxyphenyl, 4-methylphenyl, 2-fluorophenyl, 3-chlorphenyl, 2-methoxyl-4-fluorophenyl, 2, 4-difluorophenyl or 2-bromophenyl.
4. The curcumenol derivative with triazole structure of claim 1, wherein: the curcumenol derivative containing the triazole structure is any one of compounds shown as formulas C-01-C-10:
5. the curcumenol derivative containing a triazole structure as claimed in claim 1, which is used for preparing an antitumor drug.
6. The use of claim 5, wherein: the tumor cell is human colorectal cancer cell.
7. The use of claim 6, wherein: the human colorectal cancer cell is a Sw620 cancer cell.
8. The use of claim 7, wherein: the curcumenol derivative containing a triazole structure is a compound shown as a formula C-05 or C-09.
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| CN114315855A (en) * | 2022-02-09 | 2022-04-12 | 贵州省中国科学院天然产物化学重点实验室 | Curcumenol derivatives, preparation method and application thereof in preparation of anti-inflammatory drugs |
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| CN113336765A (en) * | 2021-06-16 | 2021-09-03 | 浙江工业大学 | Curcumenol esterified product, preparation method and application of curcumenol esterified product in medicine for treating colorectal cancer |
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