Tryptanthrin compound, synthetic method and application thereof

Abstract

The invention belongs to the technical field of compounds and application thereof, and relates to a tryptanthrin compound, and a synthesis method and application thereof. The tryptophan compound is a compound a, a compound b or a compound c; the structural formula of the tryptophan compound is # imgabs0, and the tryptophan compound has an inhibiting effect on tumor cells and can be used for preparing tumor treatment drugs; synthesis is simple, reaction temperature is mild, and industrial production is easy to achieve.

Description

Technical Field

[0001] The invention belongs to the technical field of compounds and their applications, and relates to a tryptanthrin compound, a synthesis method and applications thereof. Background Art

[0002] Tryptanthrin, chemically known as indole[2,1-b]quinazoline-6,12-dione, is an indolequinazoline alkaloid, presenting as yellow needle-shaped crystals at room temperature; it is mainly found in traditional Chinese medicines such as Folium Isatidis, Radix Isatidis, Indigo Naturalis (content is 0.01%-0.0065%), as well as medicinal plants such as Indigofera tinctoria, Isatis indigotica, Polygonum tinctorium (content is 0.001%, 0.003% and 0.006% respectively). The structural formula of tryptanthrin is as follows:

[0003]

[0004] Tryptanthrin is named after the use of excess L-tryptophan to cultivate Candida lipolytica, and the tryptanthrin components isolated from its metabolites. It is worth mentioning that researchers have isolated tryptanthrin from the urine of Asian elephants; other researchers have isolated tryptanthrin from the metabolites of marine Streptomyces sp. In 2007, researchers first isolated the tryptanthrin derivative ophiuroidine from the marine invertebrate Pseudothroxysphenanthellus, and determined through spectral data that the structure of the isolated compound is 4,8,9-trihydroxyindole [2,1-b] quinazoline-6,12-dione. In subsequent studies, researchers have successively isolated a variety of different tryptanthrin derivatives; however, the existing tryptanthrin derivatives are not very active in inhibiting tumors, and these problems have affected the drug development of tryptanthrin derivatives. Summary of the invention

[0005] Aiming at the technical problem that the existing tryptanthrin derivatives have weak activity in inhibiting tumors, the present invention provides a tryptanthrin compound, a synthesis method and application thereof, which has strong inhibitory activity and can be used as a raw material in the preparation of tumor drugs.

[0006] A tryptanthione compound, wherein the tryptanthione compound is compound a, compound b or compound c; the structural formula of compound a is:

[0007] Wherein: R1=H, 2-NO2, 2-Br or 2-Cl; R2=H, 8-Cl, 9-Cl, 8-Br, 9-Br, 8-F, 9-F, 8-NO2 or 8-CH3, R1 and R2 are not equivalent;

[0008] The structural formula of the compound b is:

[0009] Wherein: R=8-Cl or 8-Br;

[0010] The structural formula of the compound c is:

[0011]

[0012] Further defined, the structural formula of the compound a is:

[0013]

[0014] The structural formula of the compound b is:

[0015]

[0016] A method for synthesizing a tryptanthione compound comprises the following steps:

[0017] S1. Weigh raw material A and hydroxylamine hydrochloride, add them into methanol as solvent respectively, reflux at 70°C to 90°C, and react for 2.5h to 3.0h; after cooling to room temperature, filter, wash, and dry to obtain tryptanthrin oxime; the molar volume ratio of raw material A, hydroxylamine hydrochloride and methanol is 1mmol:1.5mmol:20.0mL; raw material A is tryptanthrin or its derivatives;

[0018] S2. Weigh tryptanthrin oxime and methyl bromoacetate respectively, add them to DMF reaction solvent, then add triethylamine, and react at room temperature for 2.0h to 3.0h. After the reaction, filter, wash, and dry to obtain compound a; the molar volume ratio of tryptanthrin oxime, methyl bromoacetate, DMF and triethylamine is 0.001mol:0.001mol:20.0mL:2.0mL.

[0019] A method for synthesizing a tryptanthione compound comprises the following steps:

[0020] S1. Preparation of hydroxylamine solution

[0021] Weigh hydroxylamine hydrochloride and isopropanol and mix them evenly. Add KOH at a temperature of 30°C to 45°C and react for 5min to 10min. After the reaction is completed, cool to 0°C in an ice bath and filter to obtain a hydroxylamine solution. The molar volume ratio of hydroxylamine hydrochloride, KOH and isopropanol is 0.028 mol: 0.028 mol: 40.0 mL.

[0022] S2, adding compound a and KOH in a molar ratio of 0.00014 mol:0.0028 mol to the hydroxylamine solution of step S1, reacting at room temperature for 0.5 h to 1.5 h, and filtering after the reaction to obtain a reaction product, i.e., compound b;

[0023] The structural formula of the compound a is:

[0024]

[0025] A method for synthesizing a tryptanthione compound comprises the following steps:

[0026] Take raw material B, toluene, 4-(1H-1,2,4-triazol-1-yl)benzaldehyde and glacial acetic acid, mix them, react at 75°C to 90°C for 5.0h to 6.0h, cool to room temperature, filter and dry to obtain the reaction product, i.e. compound c; the molar volume ratio of the raw material B, toluene, 4-(1H-1,2,4-triazol-1-yl)benzaldehyde and glacial acetic acid is 0.001mol:20.0mL:1mmol:1.5mL; the raw material B is tryptanthrin hydrazone or its derivatives.

[0027] It is further defined that the raw material B is prepared according to the following method:

[0028] Raw material A, hydrazine hydrate and methanol are mixed in a molar volume ratio of 1mmol:1.5mmol:20.0mL, and refluxed at 75°C to 85°C for 2.0h to 2.5h; after cooling to room temperature, the mixture is filtered, washed, and dried at 60°C to 65°C to obtain tryptanthrin hydrazone and its derivatives; the raw material A is tryptanthrin or its derivatives.

[0029] The application of the tryptophanone compound in the preparation of drugs for treating tumors.

[0030] It is further defined that the tumor is breast cancer or lung cancer.

[0031] It is further defined that when the tumor is lung cancer;

[0032] The compound a is The compound b is

[0033] Further defined, when the tumor is breast cancer, the compound a is:

[0034]

[0035]

[0036] The compound b is Compound c is

[0037] The beneficial effects of the present invention are:

[0038] 1. The present invention provides a series of tryptanthione compounds, namely compound a, compound b and compound c; they have an inhibitory effect on tumor cells, especially breast cancer or lung cancer, and can be used for the preparation of tumor treatment drugs.

[0039] 2. The tryptophanone compound provided by the present invention can induce apoptosis of A549 cells, promote the transformation of G0 / G1 phase cells to S phase, and inhibit the entire process of cell division.

[0040] 3. The preparation of the tryptophanone compound of the present invention adopts simple operations such as mixing and heating under reflux, and the reaction temperature is mild, which is easy to realize industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 The morphological changes of A549 cells induced by compound a8;

[0042] Figure 2 Compound a8 induces apoptosis in A549 cells;

[0043] Figure 3 Compound a8 induces A549 cell cycle changes;

[0044] Figure 4 Compound a8 induces cell cycle changes in A549 cells. DETAILED DESCRIPTION

[0045] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0046] The present invention provides a tryptanthione compound comprising compound a, compound b or compound c.

[0047] In the present invention, the synthetic route of compound a is as follows:

[0048]

[0049] Specifically, the synthesis method of compound a comprises the following steps:

[0050] S1. Weigh raw material A and hydroxylamine hydrochloride, add them into methanol as solvent respectively, reflux at 70°C to 90°C, and react for 2.5h to 3.0h; after cooling to room temperature, filter, wash, and dry to obtain tryptanthrin oxime; the molar volume ratio of raw material A, hydroxylamine hydrochloride and methanol is 1mmol:1.5mmol:20.0mL; raw material A is tryptanthrin or its derivatives;

[0051] S2. Weigh tryptanthrin oxime and methyl bromoacetate respectively, add them into DMF reaction solvent, then add triethylamine, and react at room temperature for 2.0 h to 3.0 h. After the reaction, filter, wash, and dry to obtain compound a.

[0052] The molar volume ratio of tryptanthrin oxime, methyl bromoacetate, DMF and triethylamine is 0.001 mol: 0.001 mol: 20.0 mL: 2.0 mL.

[0053] In the present invention, compound a is 14 kinds, including compound a1 to compound a14. Specifically, in compound a1, R1=R2=H; in compound a2, R1=H, R2=8-Cl; in compound a3, R1=H, R2=9-Cl; in compound a4, R1=H, R2=8-Br; in compound a5, R1=H, R2=9-Br; in compound a6, R1=H, R2=8-F; in compound a7, R1=H, R2=9-F; in compound a8, R1=H, R2=8-NO2; in compound a9, R1=H, R2=8-CH3; in compound a10, R1=2-NO2, R2=H; in compound a11, R1=2-Br, R2=8-F; in compound a12, R1=2-Br, R2=H; in compound a13, R1=2-Cl, R2=8-F; in compound a14, R1=2-Cl, R2=H.

[0054] In the present invention, the synthetic route of compound b is as follows:

[0055]

[0056] In the present invention, the synthesis method of compound b comprises the following steps:

[0057] S1. Preparation of hydroxylamine solution

[0058] Weigh hydroxylamine hydrochloride and isopropanol and mix them evenly. Add KOH at a temperature of 30°C to 45°C and react for 5min to 10min. After the reaction is completed, cool to 0°C in an ice bath and filter to obtain a hydroxylamine solution. The molar volume ratio of hydroxylamine hydrochloride, KOH and isopropanol is 0.028 mol: 0.028 mol: 40.0 mL.

[0059] S2. Add compound a and KOH in a molar ratio of 0.00014 mol:0.0028 mol to the hydroxylamine solution of step S1, and react at room temperature for 0.5 h to 1.5 h. After the reaction is completed, filter to obtain a reaction product, namely compound b.

[0060] The structural formula of compound a is:

[0061]

[0062] In the present invention, compound b is 10, including compound b1 to compound b10. Specifically, in compound b1, R=H; in compound b2, R=8-Cl; in compound b3, R=9-Cl; in compound b4, R=8-Br; in compound b5, R=9-Br; in compound b6, R=8-F; in compound b7, R=9-F; in compound b8, R=8-CH3; in compound b9, R=H; in compound b10, R=8-CH3.

[0063] In the present invention, the synthetic route of compound c is as follows:

[0064]

[0065] In the present invention, the synthesis method of compound C comprises the following steps:

[0066] Take raw material B, toluene, 4-(1H-1,2,4-triazol-1-yl)benzaldehyde and glacial acetic acid, mix them, react at 75°C to 90°C for 5.0h to 6.0h, cool to room temperature, filter and dry to obtain the reaction product, i.e., compound c.

[0067] The molar volume ratio of raw material B, toluene, 4-(1H-1,2,4-triazol-1-yl)benzaldehyde and glacial acetic acid is 0.001 mol:20.0 mL:1 mmol:1.5 mL; raw material B is tryptanthrin hydrazone or its derivative.

[0068] Further defined, raw material B is prepared according to the following method:

[0069] Raw material A, hydrazine hydrate and methanol are mixed in a molar volume ratio of 1mmol:1.5mmol:20.0mL, and refluxed at 75°C to 85°C for 2.0h to 2.5h; after cooling to room temperature, the mixture is filtered, washed, and dried at 60°C to 65°C to obtain tryptanthrin hydrazone and its derivatives; the raw material A is tryptanthrin or its derivatives.

[0070] In the present invention, compound c includes compound c1 to compound c5. Specifically, in compound c1, R=H; in compound c2, R=8-Cl; in compound c3, R=9-Cl; in compound c4, R=9-Br; in compound c5, R=8-CH3.

[0071] The tryptanthione compound provided by the present invention has the function of inhibiting the activity of lung cancer cells A549, human breast cancer cells MDA-MB-231 or human breast cancer cells MCF-7, and can be used for preparing drugs for treating lung cancer or breast cancer.

[0072] The preparation and application of several groups of specific tryptanthione compounds are used as examples to illustrate the tryptanthione compounds provided by the present invention.

[0073] It should be noted that, unless otherwise specified, the drugs and reagents used in the following examples are conventional commercially available products; unless otherwise specified, the operation steps performed in the following examples are conventional operations in the art.

[0074] Example 1. Synthesis of Tryptophanone Compound a2

[0075] This embodiment provides a method for synthesizing a tryptanthrin compound, comprising the following steps:

[0076] S1. Weigh 0.25 g (0.001 mol) of tryptanthrin or its derivatives and 0.10 g (0.0015 mol) of hydroxylamine hydrochloride, add them into a 100 mL three-necked flask with a stirrer, add 20.0 mL of methanol as solvent, reflux at 80° C., and react for 3.0 h. After the reaction is completed, cool the reaction system to room temperature and filter it, wash the filter cake with methanol to remove the residual solvent and excess hydroxylamine hydrochloride, and finally dry the filter cake after washing with methanol at 60° C. to obtain tryptanthrin oxime (or its derivatives).

[0077] The structural formula of tryptanthrin or its derivatives is: Among them, R1=H, R2=8-Cl.

[0078] S2. Take tryptanthrin oxime (or its derivatives) as the reaction raw material, weigh 0.26 g (0.001 mol) of tryptanthrin oxime (or its derivatives), 0.15 g (0.001 mol) of methyl bromoacetate, add them into a 100 mL round-bottom flask with a stirrer, use 20.0 mL of DMF as the reaction solvent, add 2.0 mL of triethylamine, react at room temperature for 2.0 h, filter after the reaction, wash the filter cake with methanol, and dry to obtain tryptanthrin compound a2.

[0079] The chemical formula of compound a2 is as follows:

[0080]

[0081] Yellow solid, 0.33 g, yield: 89.4%, melting point (mp): 233.5-234.8°C; IR (KBr): 3062, 2958, 1761, 1689, 1645, 1586, 1458, 1342, 1316, 1270, 1226, 1144, 1107, 1060, 990, 967, 903, 773 cm -1 ; 1 H NMR(400MHz,Chloroform-d)δ8.59(d,J=8.7Hz,1H),8.43–8.34(m,2H),7.94(d,J =8.2Hz,1H),7.84–7.77(m,1H),7.62–7.55(m,2H),5.17(s,2H),3.83(s,3H).ppm; 13 CNMR(101MHz,Chloroform-d)δ168.82,158.73,147.26,146.92,145.35,138.65,134.94,133.26,132.49,129 .05,128.77,128.47,127.24,122.08,119.91,118.19,77.48,77.16,76.84,73.12,52.42.ppm; MS(ESI)m / z:C 18 H 12 ClN3O4 calcd for:370.06[M+H] + ,Found:370.05.

[0082] Example 2: Synthesis of Tryptophanone Compound a3

[0083] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0084] The difference is that in this embodiment, the structural formula of tryptanthrin or its derivatives is:

[0085] Among them, R1=H, R2=9-Cl.

[0086] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0087] The chemical formula of compound a3 is as follows:

[0088]

[0089] Yellow solid, 0.28 g, yield: 75.9%, melting point (mp): 192.3-195.5°C; IR (KBr): 3627, 3545, 3117, 3091, 2991, 2951, 1741, 1694, 1647, 1586, 1462, 1426, 1360, 1321, 1233, 1150, 1117, 1060, 1028, 968, 883, 855, 775, 688, 672 cm -1 ; 1 H NMR(400MHz,Chlor oform-d)δ8.68(d,J=1.9Hz,1H),8.40(d,J=7.9Hz,1H),8.30(d,J=8.3Hz,1H),7.94(d,J=8.1Hz,1H),7 .80(t,J=7.8Hz,1H),7.58(t,J=7.4Hz,1H),7.36(dd,J=8.3,1.9Hz,1H),5.14(s,2H),3.81(s,3H).ppm; 13 C NMR(101MHz,Chloroform-d)δ168.89,158.78,147.52,146.85,145.43,140.95,139.51,135.03,129.62,129 .04,128.49,127.32,127.19,121.97,117.74,117.17,77.48,77.16,76.84,73.06,52.38ppm; MS(ESI)m / z:C 18 H 12 ClN3O4 calcd for:370.06[M+H] + ,Found:371.45.

[0090] Example 3. Synthesis of Compound a4

[0091] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0092] The difference is that in this embodiment, the structural formula of tryptanthrin or its derivatives is:

[0093] Among them, R1=H, R2=8-Br.

[0094] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0095] The chemical formula of compound a4 is as follows:

[0096]

[0097] Yellow solid, 0.38 g, yield: 91.7%, melting point (mp): 244.2-246.4 ° C; IR (KBr): 3497, 3285, 3126, 3061, 3028, 2948, 2854, 1926, 1753, 1676, 1646, 1586, 1456, 1405, 1338, 1314, 1267, 1226, 1139, 1103, 1054, 1029, 969, 890, 842, 801, 775, 690 cm -1 ; 1 H N R(400MHz,Chloroform-d)δ8.58–8.50(m,2H),8.41(dd,J=7.9,1.5Hz,1H),7.96(d,J=8.1Hz,1H),7. 81(t,J=7.3Hz,1H),7.75(dd,J=8.6,2.1Hz,1H),7.59(t,J=7.5Hz,1H),5.18(s,2H),3.83(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ168.83,158.76,147.14,146.94,145.22,139.10,136.17,134.96,131.60,129 .07,128.49,127.26,122.08,120.23,120.13,118.54,77.48,77.16,76.84,73.12,52.43ppm; MS(ESI)m / z:C 18 H 12 BrN3O4 calcd for:414.01[M+H] + ,Found:414.00.

[0098] Example 4. Synthesis of Compound a5

[0099] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0100] The difference is that in this embodiment, the structural formula of tryptanthrin or its derivatives is:

[0101] Among them, R1=H, R2=9-Br.

[0102] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0103] The chemical formula of compound a5 is as follows:

[0104]

[0105] Yellow solid, 0.23 g, yield: 79%, melting point (mp): 216.8-220.5°C; IR (KBr): 3474, 3107, 3003, 2957, 1990, 1744, 1687, 1650, 1588, 1462, 1419, 1355, 1320, 1141, 1103, 1052, 1026, 967, 886, 825, 779, 691 cm -1 ; 1 H NMR(400MHz,Chloroform-d)δ8.87(d,J=1.8Hz,1H),8.41(dd,J=8.0,1.6Hz,1H),8.24(d,J=8.2Hz,1H),7 .95(d,J=8.1Hz,1H),7.81(ddd,J=8.4,7.2,1.6Hz,1H),7.63–7.50(m,2H),5.15(s,2H),3.82(s,3H)ppm;

[0106] 13 C NMR(101MHz,Chloroform-d)δ168.85,158.75,147.39,146.85,145.55,140.89,135.02,130.17,129.73,129 .05,128.49,127.89,127.31,121.97,120.53,117.55,77.48,77.16,76.84,73.09,52.38ppm; MS(ESI)m / z:C 18 H 12 BrN3O4 calcd for:435.99[M+Na] + ,Found:436.90.

[0107] Example 5. Synthesis of Compound a6

[0108] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0109] The difference is that in this embodiment, the structural formula of tryptanthrin or its derivatives is:

[0110] Among them, R1=H, R2=8-F.

[0111] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0112] The chemical formula of compound a6 is as follows:

[0113]

[0114] Yellow solid, 0.29 g, yield: 91.9%, melting point (mp): 233.3-235.1 ° C; IR (KBr): 3493, 3343, 3123, 3078, 2963, 2939, 2861, 2113, 1985, 1907, 1837, 1757, 1685, 1586, 1476, 1382, 1350, 1312, 1245, 1130, 1055, 1015, 886, 835, 768, 739, 685 cm -1 ; 1 H NMR(400MHz,Chloroform-d)δ8.63(dd,J=8.9,4.5Hz,1H),8.41(dd,J=8.0,1.5Hz,1H),8.09(dd,J=8.0,2.7Hz,1H),7.95(d, J=8.2Hz,1H),7.80(ddd,J=8.3,7.1,1.6Hz,1H),7.62–7.54(m,1H),7.32(td,J=8.8,2.8Hz,1H),5.17(s,2H),3.82(s,3H)pp m; 13 C NMR (101MHz, Chloroform-d) δ168.79, 158.69, 146.90, 145.70 (d, J = 3.0Hz), 136.52 (d, J = 2.5Hz), 134.84, 129.01, 128. 41,127.18,122.16,120.24,120.11–119.75(m),118.47(d,J=8.1Hz),116.21,115.95,73.12,52.40ppm; MS(ESI)m / z:C 18 H 12 FN3O4calcd for:354.09[M+H] + ,Found:354.05.

[0115] Example 6. Synthesis of Compound a7

[0116] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0117] The difference is that in this embodiment, the structural formula of tryptanthrin or its derivatives is:

[0118] Among them, R1=H, R2=9-F.

[0119] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0120] The chemical formula of compound a7 is as follows:

[0121]

[0122] Yellow solid, 0.26 g, yield: 73.7%, melting point (mp): 207.9-209.0°C.

[0123] The infrared spectrum of the compound was measured by solid potassium bromide tablet method. The IR (KBr) results were: 3036, 2953, 1968, 1862, 1747, 1696, 1645, 1587, 1440, 1365, 1309, 1224, 1104, 1050, 975, 866, 778 cm -1 .

[0124] Proton spectrum of the compound: 1 H NMR (400MHz, Chloroform-d) δ8.41–8.40(m,1H), 8.40–8.38(m,1H), 8.37(dd,J=4.1, 1.5Hz, 1H), 7.94(d,J=8.1Hz, 1 H), 7.80(ddd,J=8.3,7.1,1.6Hz,1H),7.61–7.55(m,1H),7.07(td,J=8.7,2.4Hz,1H),5.14(s,2H),3.81(s,3H)ppm.

[0125] MS (ESI) m / z: C 18 H 12 FN3O4 calcd for:376.07[M+Na] + ,Found:376.05.

[0126] Example 7. Synthesis of Compound a8

[0127] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0128] The difference is that in this embodiment, the structural formula of tryptanthrin or its derivatives is:

[0129] Among them, R1=H, R2=8-NO2.

[0130] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0131] The chemical formula of compound a8 is as follows:

[0132]

[0133] Yellow solid, 0.32 g, yield: 84%, melting point (mp): 278.9-281.3 ° C; IR (KBr): 3097, 2963, 2856, 1990, 1848, 1741, 1682, 1583, 1527, 1460, 1353, 1312, 1283, 1213, 1044, 1002, 929, 849, 771, 693 cm -1 ; 1 H NMR(400MHz,Chloroform-d)δ9.21(d,J=2.3Hz,1H),8.83(d,J=8.9Hz,1H),8.54(dd,J=8.9,2.4Hz,1H),8.43(d, J=7.7Hz,1H),7.97(d,J=8.1Hz,1H),7.85(t,J=7.0Hz,1H),7.62(t,J=7.6Hz,1H),5.23(s,2H),3.85(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ168.65,159.00,147.17,146.78,146.13,144.74,144.11,135.63,129.32,129 .14,129.02,127.62,124.29,121.86,119.30,117.45,77.48,77.16,76.84,73.40,52.58ppm; MS(ESI)m / z:C 18 H 12 N4O6 calcd for:403.06[M+Na] + ,Found:403.10.

[0134] Example 8. Synthesis of Compound a9

[0135] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0136] The difference is that in this embodiment, the structural formula of tryptanthrin or its derivatives is:

[0137] Among them, R1=H, R2=8-CH3.

[0138] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0139] The chemical formula of compound a9 is as follows:

[0140]

[0141] Yellow solid, 0.34 g, yield: 94.5%, melting point (mp): 241.2-242.1°C.

[0142] IR (KBr): 3482, 3060, 2989, 2936, 2859, 1925, 1746, 1675, 1646, 1582, 1467, 1 409, 1374, 1342, 1318, 1263, 1226, 1131, 1102, 1027, 976, 882, 775, 734, 690cm -1 ; 1 H NMR(400MHz,Chloroform-d)δ8.49(d,J=8.2Hz,1H),8.40(dd,J=7.9,1.6Hz,1H),8.19–8.16(m,1H),7.94(dd,J=8.2,1.1Hz,1H),7 .78(ddd,J=8.4,7.1,1.6Hz,1H),7.55(ddd,J=8.2,7.2,1.2Hz,1H),7.43–7.37(m,1H),5.15(s,2H),3.82(s,3H),2.43(s,3H)ppm; 13 C NMR(101MHz,Chloroform-d)δ169.12,158.77,147.94,147.03,146.35,138.24,136.98,134.59,134.04,129.30 ,128.92,128.12,127.12,122.29,118.83,116.84,77.48,77.16,76.84,72.93,52.31,21.46ppm; MS(ESI)m / z:C 19 H 15 N3O4 calcd for:350.11[M+H] + ,Found:350.05.

[0143] Example 9. Synthesis of Compound a10

[0144] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0145] The difference is that in this embodiment, the structural formula of tryptanthrin or its derivatives is:

[0146] Where R1=2-NO2, R2=H

[0147] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0148] The chemical formula of compound a10 is as follows:

[0149]

[0150] Yellow solid, 0.14 g, yield: 36.8%, melting point (mp): >300°C; IR (KBr): 3090, 3029, 2933, 2853, 1760, 1731, 1685, 1601, 1523, 1462, 1349, 1321, 1220, 1138, 1067, 1002, 936, 875, 762, 709, 686 cm -1 ; 1 H NMR(400MHz,Chloroform-d)δ9.28(d,J=2.6Hz,1H),8.64(t,J=7.0Hz,1H),8.59(dd,J=8.8,2.6Hz,1H),8.41(d,J=7.8H z,1H),8.09(d,J=8.8Hz,1H),7.68(t,J=7.8Hz,1H),7.46(t,J=7.6Hz,1H),5.20(s,2H),3.83(s,3H)ppm; MS(ESI)m / z:C 18 H 12 N4O6calcd for:381.0830[M+H] + ,Found:381.0830

[0151] Example 10. Synthesis of Compound a11

[0152] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0153] The difference is that in this embodiment, the structural formula of tryptanthrin or its derivatives is:

[0154] Among them, R1=2-Br, R2=8-F.

[0155] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0156] The chemical formula of compound a11 is as follows:

[0157]

[0158] Yellow solid, 0.36 g, yield: 47.2%, melting point (mp): >300°C.

[0159] IR (KBr): 3074, 2945, 2860, 1757, 1687, 1642, 1582, 1473, 1442, 1383, 1350, 1309, 1243, 1131, 1055, 1008, 947, 888, 829, 741, 712, 672cm -1 ; 1 H NMR(400MHz,Chloroform-d)δ8.62(dd,J=8.9,4.5Hz,1H),8.54(d,J=2.3Hz,1H),8.10(dd,J=7.9,2.7Hz,1H),7.89(d d,J=8.7,2.3Hz,1H),7.81(d,J=8.7Hz,1H),7.34(td,J=8.7,2.7Hz,1H),5.17(s,2H),3.83(s,3H)ppm; MS(ESI)m / z:C 18 H 11 BrFN3O4 calcd for:431.9990[M+H] + ,Found:431.9990.

[0160] Example 11 Synthesis of Compound a12

[0161] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0162] The difference is that in this embodiment, the structural formula of tryptanthrin or its derivatives is:

[0163] Among them, R1=2-Br, R2=H.

[0164] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0165] The chemical formula of compound a12 is as follows:

[0166]

[0167] Yellow solid, 0.22 g, yield: 53.5%, melting point (mp): 249.2-249.7°C.

[0168] IR (KBr): 3067, 2948, 1752, 1691, 1640, 1580, 1461, 1359, 1324, 1227, 1139, 1106, 1055, 1030, 964, 889, 835, 781, 681cm -1 ; 1H NMR (400MHz, Chloroform-d) δ8.62(d,J=8.1Hz,1H),8.53(d,J=2.2Hz,1H),8.38(d,J=7.6Hz,1H),7.87(dd,J=8.7,2.3H z,1H),7.81(d,J=8.7Hz,1H),7.63(t,J=7.3Hz,1H),7.41(t,J=7.7Hz,1H),5.16(s,2H),3.82(s,3H)ppm; MS(ESI)m / z:C 18 H 12 BrN3O4 calcd for:414.0084[M+H] + ,Found:414.0084.

[0169] Example 12: Synthesis of Compound a13

[0170] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0171] The difference is that in this embodiment, the structural formula of tryptanthrin or its derivatives is:

[0172] Among them, R1=2-Cl, R2=8-F.

[0173] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0174] In this embodiment, the chemical formula of compound a13 is as follows:

[0175]

[0176] Compound a13 is a yellow solid, 0.11 g, yield: 28%, melting point (mp): 279.1-279.6°C. IR (KBr): 3077, 3040, 2949, 2861, 1917, 1760, 1690, 1642, 1583, 1476, 1441, 1350, 1310, 1244, 1222, 1131, 1113, 1056, 1008, 947, 829, 741, 693 cm -1 ; 1H NMR(400MHz,Chlor oform-d)δ8.62(dd,J=8.9,4.5Hz,1H),8.37(d,J=2.5Hz,1H),8.09(dd,J=8.0,2.7Hz,1H),7.89(d,J=8.7Hz ,1H),7.74(dd,J=8.7,2.5Hz,1H),7.34(td,J=8.8,2.7Hz,1H),5.17(s,2H),3.83(s,3H)ppm; MS(ESI)m / z:C 18 H 11 ClFN3O4 calcd for:388.0495[M+H] + ,Foun d:388.0495.

[0177] Example 13. Synthesis of Compound a14

[0178] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0179] The difference is that in this embodiment, the structural formula of tryptanthrin or its derivatives is:

[0180] Among them, R1=2-Cl, R2=H.

[0181] The synthesis method of the tryptanthrin compound provided in this embodiment is the same as that in Example 1.

[0182] The chemical formula of compound a14 is as follows:

[0183]

[0184] Compound a14 is a yellow solid, 0.21 g, yield: 56.5%, melting point (mp): 255.0-255.6°C. IR (KBr): 3071, 2948, 1754, 1689, 1580, 1464, 1360, 1325, 1228, 1108, 1056, 889, 873, 782, 696 cm -1 ; 1 H NMR(400MHz,Chloroform-d)δ8.64(d,J=8.1Hz,1H),8.42–8.37(m,2H),7.90(d,J=8.7Hz,1H),7.73(dd,J= 8.7,2.5Hz,1H),7.64(t,J=7.2Hz,1H),7.42(t,J=7.7Hz,1H),5.17(s,2H),3.82(s,3H)ppm; MS(ESI)m / z:C 18 H12 ClN3O4 calcd for:370.0589[M+H] + ,Found:370.0589.

[0185] Example 14. Synthesis of Compound b2

[0186] The synthesis method of the tryptanthione compound provided in this embodiment comprises the following steps:

[0187] S1. Preparation of hydroxylamine solution: Add 1.96 g (0.028 mol) of hydroxylamine hydrochloride to a 100 mL round-bottom flask equipped with a stirrer, add 40.0 mL of isopropanol and stir to dissolve, heat the solution to 40°C, add 1.58 g (0.028 mol) of KOH, react for 10 min, cool to 0°C in an ice bath after the reaction is complete, filter, and obtain the hydroxylamine solution required for the reaction.

[0188] S2. Weigh 0.05 g (0.00014 mol) of compound a2, add it into a 100 mL round-bottom flask with a built-in stirrer, add the filtered hydroxylamine solution, then add 0.15 g (0.0028 mol) of KOH, react at room temperature for 1.0 h, and filter to obtain the reaction product after the reaction is completed.

[0189] In this example, the synthesis process of compound a2 refers to the synthesis method of Example 1.

[0190] In this embodiment, the structural formula of compound b2 is:

[0191]

[0192] Compound b2 is a yellow solid, 0.015 g, yield: 28%, melting point (mp): >300°C.

[0193] IR (KBr) of compound b2: 3499, 3251, 3127, 3085, 2935, 2852, 1699, 1643, 1605, 1455, 1338, 1316, 1140, 1070, 1033, 982, 912, 832, 768, 672 cm -1 .

[0194] Compound b2 1 H NMR(400MHz,DMSO-d6)δ8.51(d,J=8.7Hz,1H),8.32–8.26(m,2H),7.94–7.85(m,2H ), 7.77 (dd, J=8.6, 2.3Hz, 1H), 7.64 (ddd, J=8.2, 6.6, 1.7Hz, 1H), 4.70 (s, 2H) ppm.

[0195] MS (ESI) of compound b2 m / z: C 17 H 11 ClN4O4 calcd for:371.05[M+H] + ,Found:371.15.

[0196] Example 15. Synthesis of Compound b4

[0197] The synthesis method of the tryptanthione compound provided in this embodiment comprises the following steps:

[0198] S1. Preparation of hydroxylamine solution: Add 1.96 g (0.028 mol) of hydroxylamine hydrochloride to a 100 mL round-bottom flask equipped with a stirrer, add 40.0 mL of isopropanol and stir to dissolve, heat the solution to 40°C, add 1.58 g (0.028 mol) of KOH, react for 10 min, cool to 0°C in an ice bath after the reaction is complete, filter, and obtain the hydroxylamine solution required for the reaction.

[0199] S2. Weigh 0.05 g (0.00014 mol) of compound a4, add it into a 100 mL round-bottom flask with a built-in stirrer, add the filtered hydroxylamine solution, and then add 0.15 g (0.0028 mol) of KOH. React at room temperature for 1.0 h. After the reaction is completed, filter to obtain the reaction product.

[0200] In this example, the synthesis process of compound a4 refers to the synthesis method of Example 1.

[0201] In this embodiment, the structural formula of compound b4 is:

[0202]

[0203] Compound b4 is a yellow solid, 0.0184 g, yield: 31.7%, melting point (mp): >300°C.

[0204] IR (KBr) of compound b4: 3257, 2936, 1918, 1699, 1645, 1606, 1452, 1429, 1337, 1141, 1034, 983, 911, 878, 831, 770, 686, 669 cm -1 .

[0205] Compound b4 1H NMR (400MHz, DMSO-d6) δ8.46(d,J=8.6Hz,1H),8.41(d,J=2.1Hz,1H),8.30(dd,J=7. 9,1.4Hz,1H),7.94–7.82(m,3H),7.64(ddd,J=8.2,6.6,1.7Hz,1H),4.69(s,2H)ppm.

[0206] MS (ESI) of compound b4 m / z: C 17 H 11 BrN4O4 calcd for:415.00[M+H] + ,Found:415.00.

[0207] Example 16. Synthesis of Compound c1

[0208] The synthesis method of the tryptanthione compound provided in this embodiment comprises the following steps:

[0209] S1. Weigh 0.25 g (0.001 mol) of tryptanthrin (or its derivative) and 0.08 g (0.0015 mol) of hydrazine hydrate, add them into a 100 mL three-necked flask with a built-in stirrer, add 20.0 mL of methanol as solvent, and reflux at 80° C. for 2.0 h. After the reaction is completed, the reaction system is cooled to room temperature and filtered, and the filter cake is washed with methanol to remove the residual solvent and excess hydrazine hydrate, and finally the washed filter cake is dried at 60° C. to obtain tryptanthrin hydrazone and its derivatives.

[0210] S2. Weigh 0.26 g (0.001 mol) of tryptanthrin hydrazone (or its derivatives), add it into a 100 mL three-necked flask with a built-in stirring bar, add 20.0 mL of toluene as a reaction solvent, add 0.17 g (0.001 mol) of 4-(1H-1,2,4-triazol-1-yl)benzaldehyde, add 1.5 mL of glacial acetic acid, react at 85 ° C for 6.0 h, cool to room temperature after the reaction, filter, dry and recrystallize with anhydrous ethanol to obtain the reaction product.

[0211] In this embodiment, the structural formula of compound c1 is:

[0212]

[0213] The compound of this example is a brown solid, 0.19 g, with a yield of 45.6%, and a melting point (mp): 247.3-248.1°C.

[0214] IR (KBr) of the compounds in this example: 3117, 3056, 1754, 1682, 1602, 1522, 1460, 1404, 1356, 1321, 1278, 1233, 1179, 1145, 1107, 1048, 979, 949, 872, 832, 773, 687, 671 cm -1 .

[0215] The compound of this example 1 H NMR (400MHz, DMSO-d6) δ9.48(s,1H),8.91(s,1H),8.57(d,J=8.1Hz,1H),8.50(d,J=7.9Hz,1H),8.33(d,J=6.7Hz,2H),8.2 6(d,J=8.3Hz,2H),8.13(d,J=8.3Hz,2H),7.90(d,J=20.4Hz,2H),7.71(dt,J=19.6,7.2Hz,2H),7.51(t,J=7.6Hz,1H)ppm.

[0216] MS (ESI) m / z of the compound in this example: C 24 H 15 N7O calculated for:418.1411[M+H] + ,Found:418.1411.

[0217] Furthermore, the antibacterial activity of the tryptophanone compounds prepared and synthesized in Examples 1 to 17 above was verified.

[0218] Test 1

[0219] In this study, lung cancer cells A549, human breast cancer cells MDA-MB-231 or human breast cancer cells MCF-7 were used as cell samples to determine the IC values ​​of the above 17 compounds on each cell type. 50 value.

[0220] In this experiment, in order to illustrate the anti-cancer performance of the tryptanthrin compound of the present invention, tryptanthrin, gefitinib and tamoxifen were compared.

[0221] The test results are shown in Table 1.

[0222] Table 1 IC values ​​of various compounds against cancer cells 50 value

[0223]

[0224]

[0225]

[0226] It can be seen from Table 1 that compared with the control group, the compounds a2, a4, a8, a11, a13, b2 and b4 provided by the present invention all showed good inhibitory effects on lung cancer cells A549.

[0227] It can be seen from Table 1 that compared with the control group, the compounds a3 to a14 and compound c1 provided by the present invention all showed good inhibitory effects on human breast cancer cells MDA-MB-231.

[0228] It can be seen from Table 1 that compared with the control group, the compounds a2, a8, a12, a13, a14 and b4 provided by the present invention all showed good inhibitory effects on human breast cancer cells MCF-7.

[0229] Experiment 2 Compound a8 induces A549 cells

[0230] In this experiment, compound a8 was used to induce A549 cells.

[0231] Induction process: A549 cells were seeded on glass-bottomed dishes (seeding density was 0.2×106 cells), 2 mL of culture medium (Ham's F-12K medium + 10% FBS) was added to each well and placed in a 37°C, 5% CO2 incubator for 24 hours. After 24 hours, the culture medium in the 6-well plate was discarded, and 2 mL of different concentrations of drug solution were added (according to the results of the MTT experiment, the drug concentration was adjusted to 6.25, 3.125, 1.5625, 0.78125, 0.1953125, 0.09765625 μmol / L), and the culture was continued for 24 hours. After 24 hours, the culture medium in the dish was discarded, and the cells were washed twice with PBS buffer solution, each time for 3 minutes. 2 mL of 4% paraformaldehyde was added to each dish, and the cells were fixed at room temperature for 15 minutes. The 4% paraformaldehyde in the dish was discarded, and 2 mL of PBS buffer was added to each dish for washing, each time for 3 minutes, and washed 3 times. The liquid in the dish was discarded, and 1 mL of 10 μg / mL Hoechst 33342 dye solution was added to each dish, and the dish was placed at room temperature for 5 min, and then washed with PBS 3 times, each time for 3 min. Finally, the morphological changes of the cells were observed using a laser confocal microscope at 405 nm.

[0232] In the above experiment, the morphological changes of A549 cells induced by compound a8 were monitored, and the results were as follows: Figure 1 shown.

[0233] Figure 1In the figures, a is the blank control group; b is 0.09 μmol / L gefitinib; c is 6.25 μmol / L gefitinib; d is 0.09 μmol / L compound a8; e is 3.12 μmol / L compound a8; and f is 6.25 μmol / L compound a8.

[0234] from Figure 1 It can be seen that the cell nucleus stained with Hoechst 33342 is blue. Figure a is a blank control group, and the cell nucleus is a regular circle or oval; Figure b and Figure c are 0.09μM and 6.25μM gefitinib positive control groups, respectively. In Figure b and Figure c, a certain amount of cell nucleus morphology has undergone irregular changes or cell nucleus lysis fragments have appeared, indicating that gefitinib has caused chromatin shrinkage or cell nucleus lysis in the A549 cell nucleus; Figures d to f are experimental groups treated with 0.09μM, 3.12μM and 6.25μM compound a8, respectively. It can be seen that A549 cells treated with different concentrations of compound a8 have irregular cell nucleus deformation, cell nucleus shrinkage, and some cell nuclei are significantly enlarged, and cell nucleus lysis fragments can be observed, and these characteristics show concentration dependence. The above experimental results show that compound a8 can induce apoptosis of A549 cells.

[0235] Test 3

[0236] In this experiment, compound a8 was used to verify the apoptosis of A549 cells.

[0237] Apoptosis and cycle process: After treatment, A549 cells were evenly inoculated on a 6-well plate for the experiment, with an inoculation density of 0.2×106 cells per well. After inoculation, 2 mL of culture medium (Ham's F-12K medium + 10% FBS) was added to each well and placed in a 37°C, 5% CO2 incubator for 24 hours. After 24 hours, the culture medium in the 6-well plate was discarded, and 2 mL of drugs of different concentrations were added (according to the results of the MTT experiment, the drug concentration was adjusted to 6.25, 3.125, 1.5625, 0.78125, 0.1953125, 0.09765625 μmol / L), and the culture was continued for 24 hours. Three replicate wells were set for the drug addition group. After 24 hours of culture, the cells in the wells were collected, washed twice with pre-cooled cell staining buffer solution, centrifuged at 4°C, 500g, and then resuspended in 1 mL of Annexin VBindingBuffer. Then, take out 100 μL of the cell suspension and transfer it to a 1.5 mL ep tube, then add 5 μL of APC Annexin V and 10 μL of propidium iodide solution to the ep tube. Vortex the entire system and incubate the ep tube at room temperature in the dark for 15 minutes. After the incubation, add an appropriate amount of Annexin V Binding Buffer to each ep tube, and then use a flow cytometer for detection.

[0238] In this experiment, the apoptosis results of compound a8 on A549 cells are as follows: Figure 2 shown.

[0239] Figure 2 In the figures, a is the control group; b is 6.25 μmol / L gefitinib; c is 1.56 μmol / L compound a8; d is 3.125 μmol / L compound a8; and e is 6.25 μmol / L compound a8.

[0240] from Figure 2 It can be seen that compared with the blank control, after the cells were treated with different concentrations of compound a8 for 24 hours, the total apoptosis rate of each group increased to varying degrees. Specifically, when the cells were treated with three different concentrations of compound a8 of 1.5625 μmol / L, 3.25 μmol / L and 6.25 μmol / L, the apoptosis rates of the experimental groups were 0.216%, 0.94% and 9.25%, respectively, and the apoptosis rate of the blank control group was 0.216%. This shows that compound a8 can induce apoptosis of A549 cells and exhibits concentration dependence. Compared with the positive control drug gefitinib, the apoptosis rate of the positive control drug gefitinib was 0.4% when the concentration was 6.25 μmol / L. At the same concentration, the effect of compound a8 inducing A549 apoptosis was better than that of the positive control drug gefitinib.

[0241] In this experiment, the effects of compound a8 on the cell cycle of A549 cells were as follows: Figure 3 and 4 shown.

[0242] After treatment, A549 cells were seeded in 6-well plates for experiments, with a seeding density of 0.2×10 6 After inoculation, 2 mL of culture medium (Ham's F-12K culture medium + 10% FBS) was added to each well and placed in a 37°C, 5% CO2 incubator for 24 hours. After 24 hours, the culture medium in the 6-well plate was discarded, and 2 mL of different concentrations of drug solution were added (according to the results of the MTT experiment, the drug concentration was adjusted to 6.25, 3.125, 1.5625, 0.78125, 0.1953125, 0.09765625 μmol / L), and the culture was continued for 24 hours. Three replicate wells were set for the drug addition group. After 24 hours of culture, the cells in the wells were collected, 1 mL of pre-cooled 70% ethanol was added, and the mixture was gently blown and mixed, and cultured at 4°C for 24 hours. After 24 hours, centrifuge at 500g for 5 minutes, aspirate the supernatant, and then add 1 mL of pre-cooled PBS buffer solution to resuspend the cells. The cells were centrifuged again, the supernatant was aspirated, and 0.5 mL of propidium iodide staining solution was added to the centrifuge tube containing the cell pellet. The mixture was slowly pipetted to mix the cell suspension. Finally, the mixed cell suspension was incubated at 37°C in the dark for 0.5 h. After incubation, it was detected by flow cytometry.

[0243] Test results such as Figure 3 , Figure 4 And as shown in Table 2. Figure 3 In the figures, a is the control group; b is 6.25 μmol / L gefitinib; c is 1.56 μmol / L compound a8; d is 3.125 μmol / L compound a8; and e is 6.25 μmol / L compound a8.

[0244] Table 2 Change rate of A549 cells induced by compound a8

[0245] Control Group Gefitinib 3.125μmol / L 6.25μmol / L G1(％) 75.89 66.3 70.26 19.82 S(％) 9.99 17.67 12.61 26.14 G2(％) 11.93 14.26 13.56 21.06

[0246] from Figure 3 and 4It can be seen that after treating A549 cells with different concentrations of compound a8 for 24 hours, the distribution of the experimental group in the G0 / G1 phase, S phase and G2 / M phase changed significantly compared with the blank control group, especially under high concentration conditions. When the concentration of compound a8 was 6.25 μmol / L, the proportion of G0 / G1 phase cells decreased sharply from 75.89% to 19.82%, indicating that compound a8 can promote the transformation of G0 / G1 phase cells to S phase, while the proportion of S phase and G2 / M phase cells increased from 9.99% and 11.93% to 26.14% and 21.06%, respectively, indicating that most of the cells stayed in the S phase and G2 / M phase, thereby inhibiting the entire cell division process.

[0247] Obviously, the above embodiments are only for the purpose of clearly illustrating the technical solution of the present invention, and are not intended to limit the implementation methods. For ordinary technicians in the relevant field, other different forms of changes or modifications based on the above description of the present invention still fall within the protection scope of the present invention.

Claims

1. A tryptanthione compound, characterized in that The tryptophanone compound is compound a, compound b or compound c; the structural formula of compound a is: Wherein: R1=H, 2-NO2, 2-Br or 2-Cl; R2=H, 8-Cl, 9-Cl, 8-Br, 9-Br, 8-F, 9-F, 8-NO2 or 8-CH3, R1 and R2 are not equivalent; The structural formula of the compound b is: Wherein: R=8-Cl or 8-Br; The structural formula of the compound c is:

2. The tryptanthione compound according to claim 1, characterized in that The structural formula of the compound a is: The structural formula of the compound b is:

3. A method for synthesizing a tryptanthione compound as claimed in claim 1, characterized in that: The following steps are involved: S1. Weigh raw material A and hydroxylamine hydrochloride, add them into methanol as solvent respectively, reflux at 70°C to 90°C, and react for 2.5h to 3.0h; after cooling to room temperature, filter, wash, and dry to obtain tryptanthrin oxime; the molar volume ratio of raw material A, hydroxylamine hydrochloride and methanol is 1mmol:1.5mmol:20.0mL; raw material A is tryptanthrin or its derivatives; S2. Weigh tryptanthrin oxime and methyl bromoacetate respectively, add them to DMF reaction solvent, then add triethylamine, and react at room temperature for 2.0h to 3.0h. After the reaction, filter, wash, and dry to obtain compound a; the molar volume ratio of tryptanthrin oxime, methyl bromoacetate, DMF and triethylamine is 0.001mol:0.001mol:20.0mL:2.0mL.

4. A method for synthesizing a tryptanthione compound as claimed in claim 1, characterized in that: The following steps are involved: S1. Preparation of hydroxylamine solution Weigh hydroxylamine hydrochloride and isopropanol and mix them evenly. Add KOH at a temperature of 30°C to 45°C and react for 5min to 10min. After the reaction is completed, cool to 0°C in an ice bath and filter to obtain a hydroxylamine solution. The molar volume ratio of hydroxylamine hydrochloride, KOH and isopropanol is 0.028 mol: 0.028 mol: 40.0 mL. S2, adding compound a and KOH in a molar ratio of 0.00014 mol:0.0028 mol to the hydroxylamine solution of step S1, reacting at room temperature for 0.5 h to 1.5 h, and filtering after the reaction to obtain a reaction product, i.e., compound b; The structural formula of the compound a is:

5. A method for synthesizing a tryptanthione compound as claimed in claim 1, characterized in that: The following steps are involved: Take raw material B, toluene, 4-(1H-1,2,4-triazol-1-yl)benzaldehyde and glacial acetic acid, mix them, react at 75°C to 90°C for 5.0h to 6.0h, cool to room temperature, filter and dry to obtain the reaction product, i.e. compound c; the molar volume ratio of the raw material B, toluene, 4-(1H-1,2,4-triazol-1-yl)benzaldehyde and glacial acetic acid is 0.001mol:20.0mL:1mmol:1.5mL; the raw material B is tryptanthrin hydrazone or its derivatives.

6. The method for synthesizing a tryptophanone compound according to claim 5, characterized in that: The raw material B is prepared according to the following method: Raw material A, hydrazine hydrate and methanol are mixed in a molar volume ratio of 1mmol:1.5mmol:20.0mL, and refluxed at 75°C to 85°C for 2.0h to 2.5h; after cooling to room temperature, the mixture is filtered, washed, and dried at 60°C to 65°C to obtain tryptanthrin hydrazone and its derivatives; the raw material A is tryptanthrin or its derivatives.

7. Use of the tryptophanone compound as claimed in claim 2 in the preparation of drugs for treating tumors.

8. The use according to claim 7, characterized in that: The tumor is breast cancer or lung cancer.

9. The use according to claim 8, characterized in that: The lung cancer is lung cancer cell A549 or human breast cancer cell MDA-MB-231; The compound a is The compound b is 10. The use according to claim 8, characterized in that: The breast cancer is human breast cancer cell MCF-7; The compound a is: The compound b is Compound c is

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