5, 9-di-tert-butyl naphtho-indolizino phenothiazine compound as well as preparation method and application thereof

Abstract

The invention relates to a 5, 9-di-tert-butyl naphtho-indolizine phenothiazine compound as well as a preparation method and medical application thereof. The compound is efficiently synthesized through Ullmann coupling and palladium-catalyzed intramolecular arylation reaction. In-vitro anti-tumor activity research shows that the compound has remarkable selective inhibitory activity on various human tumor cell lines, and particularly, the inhibitory effect on non-small cell lung cancer A549 cells (IC50 = 0.21 mu M) is improved by two orders of magnitude compared with that of cis-platinum; iC50 (half maximal inhibitory concentration) of other cell lines are as follows: 1.26 mu M of prostate cancer PC-3 cells, 6.78 mu M of liver cancer HepG2 cells, 7.99 mu M of cervical cancer Hela cells and 25.46 mu M of breast cancer MCF-7 cells. Preliminary toxicity experiments prove that the compound has the characteristic of low cytotoxicity. The compound can be used as a novel high-efficiency low-toxicity anti-tumor lead compound, and provides an important structural basis for the development of anti-cancer drugs.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular to a 5,9-di-tert-butylnaphthoindolizine-phenothiazine compound, a preparation method and an application thereof. Background Art

[0002] Phenothiazine, as a sulfur-nitrogen heterocyclic molecular skeleton, has become an important building block in multidisciplinary research due to its unique electronic structure and excellent chemical modifiability. [S. Revoju, A. Matuhina, L. Canil, H. Salonen, A. Hiltunen, A. Abate, P. Vivo, J. Mater. Chem. C., 2020, 8, 15486-15506; G. Lingamallu, S. G. Palivela, G. Reddy, S. Prasanthkumar, Phys. Chem. Chem. Phys., 2021, 23, 14969-14996.] For example, in the field of optoelectronic materials, phenothiazine derivatives are often used as donor units in the molecular engineering of highly conjugated donor-acceptor materials due to the synergistic effect of sulfur and nitrogen atoms, which endows the molecule with strong electron-donating properties. [J. Luo, Z. Wan, C. Jia, Chin. Chem. Lett., 2016, 27, 1304-1318.] In the field of catalysis, phenothiazine derivatives have been successfully applied in many important reaction systems as efficient photoredox catalysts, including but not limited to: metal-free atom transfer radical polymerization (ATRP), [R. M. Pearson, C.-H. Lim, B. G. McCarthy, C. B. Musgrave, G. M. Miyake, J. Am. Chem. Soc., 2016, 138, 11399-11407.] radical dehalogenation reaction, [E. H. Discekici, N. J. Treat, S. O. Poelma, K. M. Mattson, Z. M. Hudson, Y. Luo, C. J. Hawker, J. R. de Alaniz, Chem. Commun., 2015, 51, 11705-11708.] nucleophilic alkoxylation of alkyl olefins, [F. Speck, D. Rombach, H.-A. Wagenknecht, Beilstein J. Org. Chem., 2019, 15, 52-59.] photoredox catalyzed C-N bond formation reaction and C-H / C-H cross-coupling reaction, etc. [Y. Zhao, B. Huang, C. Yang, W. Xia, Org. Lett., 2016, 18, 3326-3329; S. Shibutani, K. Nagao, H. Ohmiya, Org. Lett., 2021, 23, 1798-1803.]

[0003] Current functionalization research on phenothiazine derivatives mainly focuses on four classic modification sites: (1) substitution reactions such as alkylation / arylation at the N-10 site; (2) controlled oxidation at the S-5 site to generate sulfoxide / sulfone derivatives; (3) electrophilic substitution reactions at the C-3,7 site (such as formylation, halogenation, etc.) and subsequent coupling reactions such as Suzuki and Buchwald-Hartwig to achieve structural expansion. [T.Matsuzawa, T.Hosoya, S.Yoshida, Org.Lett., 2021, 23, 2347-2352.] This limited functionalization strategy has, to a certain extent, restricted the performance optimization and functional innovation of phenothiazine materials. It is worth noting that the research on constructing extended phenothiazine systems through the π conjugation extension strategy is still in its early stages. Existing work focuses on the synthesis of new compounds and the characterization of their basic physicochemical properties. However, the derivatives developed based on this strategy are still blank in the field of biomedicine (especially anticancer activity research) and need to be further explored. Summary of the Invention

[0004] Based on the above content, the present invention provides a 5,9-di-tert-butylnaphthoindolizine-phenothiazine compound and a preparation method and application thereof.

[0005] One of the technical solutions of the present invention is a 5,9-di-tert-butylnaphthoindolizine-phenothiazine compound, the structural formula of which is shown in formula (I):

[0006]

[0007] The second technical solution of the present invention is a method for preparing the above-mentioned 5,9-di-tert-butyl naphthoindolizine-phenothiazine compound, comprising the following steps: using a 1,9-dibromo-3,7-di-tert-butyl-10-(naphthalene-1-yl)-10H-phenothiazine compound represented by formula (II) as a raw material, in the presence of palladium acetate, tricyclohexylphosphine tetrafluoroborate, and anhydrous potassium carbonate, and using anhydrous dimethylacetamide as a solvent, heating the reaction at 160° C. for 24 hours to obtain the obtained compound;

[0008] Structural formula (II)

[0009]

[0010] Reaction equation:

[0011]

[0012] Furthermore, the molar ratio of the 1,9-dibromo-3,7-di-tert-butyl-10-(naphthalen-1-yl)-10H-phenothiazine compound, palladium acetate, tricyclohexylphosphine tetrafluoroborate, and anhydrous potassium carbonate is 1:0.2:0.4:6.

[0013] Furthermore, the heating reaction also includes water washing, dichloromethane extraction, drying filtration, concentration, and purification processes after the reaction is completed; the purification is performed by silica gel column chromatography (eluent is n-hexane: dichloromethane = 50 / 1, V / V).

[0014] Furthermore, the preparation of the 1,9-dibromo-3,7-di-tert-butyl-10-(naphthalene-1-yl)-10H-phenothiazine compound represented by formula (II) includes: using the 1,9-dibromo-3,7-di-tert-butyl-10H-phenothiazine compound represented by formula (III) and 1-iodonaphthalene as raw materials, in the presence of cuprous iodide, 18-crown ether-6, and anhydrous potassium carbonate, and using anhydrous 1,2-dichlorobenzene as a solvent, heating the reaction at 180° C. for 48 hours to obtain the obtained compound;

[0015] Formula (III)

[0016]

[0017] Reaction equation:

[0018]

[0019] Furthermore, the heating reaction also includes water washing, dichloromethane extraction, drying and filtering, concentration, and purification processes after the reaction is completed; the purification is performed by silica gel column chromatography separation and purification (the eluent is n-hexane).

[0020] The third technical solution of the present invention is the use of the above-mentioned 5,9-di-tert-butylnaphthoindolizine-phenothiazine compound in the preparation of anticancer drugs.

[0021] Furthermore, the anticancer drug is used to treat human non-small cell lung cancer (A549).

[0022] Furthermore, the anticancer drug is used to treat human prostate cancer (PC-3).

[0023] Furthermore, the anticancer drug is used to treat human liver cancer (HepG2).

[0024] Furthermore, the anticancer drug is used to treat human cervical cancer (HeLa).

[0025] Furthermore, the anticancer drug is used to treat human breast cancer (MCF-7).

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The present invention constructs an extended phenothiazine compound based on the π conjugated extension strategy, and synthesizes a π conjugated extended phenothiazine derivative through the Ullmann reaction and palladium-catalyzed intramolecular arylation reaction. The 5,9-di-tert-butylnaphthoindolizine-phenothiazine compound prepared by the present invention exhibits significant selective inhibitory activity against various human cancer cell lines: IC inhibition of non-small cell lung cancer A549 cells s0 The IC value was 0.21 μM for prostate cancer PC-3 cells. 50 The value is 1.26 μM, and the IC value for HepG2 cells is s0 The value is 6.78 μM, and the IC value for cervical cancer Hela cells is 50 The IC value was 7.99 μM for breast cancer MCF-7 cells. 50 The value is 25.46μM. Compared with the commonly used clinical chemotherapy drug cisplatin, this compound showed a more significant proliferation inhibition effect on the above tumor cell lines, among which the inhibitory effect on the human non-small cell lung cancer A549 cell line was particularly prominent, with its IC 50 The value is two orders of magnitude lower than that of cisplatin. Furthermore, preliminary toxicity experiments indicate that the compound exhibits low cytotoxicity, demonstrating promising potential for development as an anticancer drug. This research provides an important structural foundation for the development of new, highly effective, and low-toxic anticancer drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a hydrogen nuclear magnetic resonance spectrum of the 5,9-di-tert-butylnaphthoindolizine-phenothiazine compound prepared in Example 1 of the present invention;

[0029] Figure 2 This is the carbon NMR spectrum of the 5,9-di-tert-butylnaphthoindolizine-phenothiazine compound prepared in Example 1 of the present invention;

[0030] Figure 3 This is the single crystal diffraction pattern of the 5,9-di-tert-butylnaphthoindolizine-phenothiazine compound prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0031] The present invention is described in detail below with reference to specific embodiments.

[0032] Example 1

[0033] Synthesis of 1,9-dibromo-3,7-di-tert-butyl-10-(naphthalen-1-yl)-10H-phenothiazine

[0034] To a 38 mL pressure-resistant reaction flask, 1,9-dibromo-3,7-di-tert-butyl-10H-phenothiazine (0.93 g, 2 mmol), 1-iodonaphthalene (1.02 g, 4 mmol), cuprous iodide (0.08 g, 0.4 mmol), 18-crown-6 (0.11 g, 0.4 mmol), and anhydrous potassium carbonate (0.41 g, 3 mmol) were added in sequence. Under argon, anhydrous 1,2-dichlorobenzene (2 mL) was added and bubbling was continued for 3 minutes. The mixture was stirred at 180°C for 48 hours. After the reaction, the mixture was cooled to room temperature, and dichloromethane (50 mL) was added. The mixture was washed three times with water, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated to dryness. The crude product was purified by silica gel column chromatography (eluent: n-hexane) to obtain the desired product (0.75 g, light yellow solid, 63% yield).

[0035] 1 H NMR (600MHz, CD2Cl2, 298K) δ7.96-7.94 (m, 1H), 7.73 (d, J=8.4Hz, 1H), 7.70-7.68 (m, 1H), 7.58-7.56 (m, 1H), 7.54-7.53 (m, 1H), 7.40 (d, J=7 .8Hz, 1H), 7.28 (t, J=7.8Hz, 1H), 7.23-7.16 (m, 2H), 7.01 (t, J=7.8HZ, 1H), 6.75-6.68 (m, 1H), 1.33, (d, J=3.0HZ, 18H). HRMS (ESI) m / z: [M+H + ]calcd.For C 30 H 30 NSBr2, 594.0466; found, 594.0461.

[0036] Example 2

[0037] Synthesis of 1,9-dibromo-3,7-di-tert-butyl-10-(naphthalen-1-yl)-10H-phenothiazine

[0038] To a 38 mL pressure-resistant reaction flask, 1,9-dibromo-3,7-di-tert-butyl-10H-phenothiazine (1.4 g, 3 mmol), 1-iodonaphthalene (1.52 g, 6 mmol), cuprous iodide (0.11 g, 0.6 mmol), 18-crown-6 (0.17 g, 0.6 mmol), and anhydrous potassium carbonate (0.62 g, 4.5 mmol) were added in sequence. Under argon, anhydrous 1,2-dichlorobenzene (3 mL) was added and bubbling was continued for 3 minutes. The mixture was stirred at 180°C for 48 hours. After the reaction, the mixture was cooled to room temperature, and dichloromethane (50 mL) was added. The mixture was washed three times with water, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated to dryness. The crude product was purified by silica gel column chromatography (eluent: n-hexane) to obtain the desired product (1.13 g, light yellow solid, 64% yield).

[0039] 1 H NMR (600MHz, CD2Cl2, 298K) δ7.96-7.94 (m, 1H), 7.73 (d, J=8.4Hz, 1H), 7.70-7.68 (m, 1H), 7.58-7.56 (m, 1H), 7.54-7.53 (m, 1H), 7.40 (d, J=7 .8Hz, 1H), 7.28 (t, J=7.8Hz, 1H), 7.23-7.16 (m, 2H), 7.01 (t, J=7.8Hz, 1H), 6.75-6.68 (m, 1H), 1.33, (d, J=3.0Hz, 18H). HRMS (ESI) m / z: [M+H + ]calcd.For C 30 H 30 NSBr2, 594.0466; found, 594.0461.

[0040] Example 3

[0041] Synthesis of 1,9-dibromo-3,7-di-tert-butyl-10-(naphthalen-1-yl)-10H-phenothiazine

[0042] To a 38 mL pressure-resistant reaction flask, 1,9-dibromo-3,7-di-tert-butyl-10H-phenothiazine (1.87 g, 4 mmol), 1-iodonaphthalene (2.04 g, 8 mmol), cuprous iodide (0.15 g, 0.8 mmol), 18-crown-6 (0.22 g, 0.8 mmol), and anhydrous potassium carbonate (0.82 g, 6 mmol) were added in sequence. Under argon, anhydrous 1,2-dichlorobenzene (4 mL) was added and bubbling was continued for 3 minutes. The mixture was stirred at 180°C for 48 hours. After the reaction, the mixture was cooled to room temperature, and dichloromethane (50 mL) was added. The mixture was washed three times with water, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated to dryness. The crude product was purified by silica gel column chromatography (eluent: n-hexane) to obtain the desired product (1.5 g, light yellow solid, 63% yield).

[0043] 1 H NMR (600MHz, CD2Cl2, 298K) δ7.96-7.94 (m, 1H), 7.73 (d, J=8.4Hz, 1H), 7.70-7.68 (m, 1H), 7.58-7.56 (m, 1H), 7.54-7.53 (m, 1H), 7.40 (d, J=7 .8Hz, 1H), 7.28 (t, J=7.8Hz, 1H), 7.23-7.16 (m, 2H), 7.01 (t, J=7.8Hz, 1H), 6.75-6.68 (m, 1H), 1.33, (d, J=3.0Hz, 18H). HRMS (ESI) m / z: [M+H + ]calcd.For C 30 H 30 NSBr2, 594.0466; found, 594.0461.

[0044] Example 4

[0045] Synthesis of 5,9-di-tert-butylnaphthoindolizine-phenothiazine compounds

[0046] To a 38 mL pressure-resistant reaction flask, 1,9-dibromo-3,7-di-tert-butyl-10-(naphthalen-1-yl)-10H-phenothiazine (0.2 g, 0.34 mmol), palladium acetate (0.02 g, 0.07 mmol), tricyclohexylphosphine tetrafluoroborate (0.05 g, 0.14 mmol), and anhydrous potassium carbonate (0.28 g, 2 mmol) were added sequentially. Under argon, anhydrous dimethylacetamide (2 mL) was added and bubbled continuously for 3 minutes. The mixture was stirred at 160°C for 24 hours. After the reaction, the mixture was cooled to room temperature, and dichloromethane (50 mL) was added. The mixture was washed three times with water, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated to dryness. The crude product was purified by silica gel column chromatography (eluent: n-hexane:dichloromethane = 50 / 1, v / v) to obtain the desired product (0.08 g, yellow solid, 54% yield).

[0047] 1 H NMR (600MHz, CDCl3, 298K) δ8.02 (d, J=9.0Hz, 1H), 7.99 (d, J=7.8Hz, 1H), 7.90 (d, J=7.8Hz, 1H), 7.87 (d, J=1.2Hz, 1H), 7.73 (d, J= 1.2Hz, 1H), 7.68 (t, J=7.8Hz, 1H), 7.58 (d, J=9.0Hz, 1H), 7.16 (d, J=1.2Hz, 1H), 7.06 (d, J=1.2Hz, 1H), 1.45 (s, 9H), 1.42 (s, 9H); 13 C NMR (150MHz, CDCl3, 298K) δ147.7, 147.4, 132.0, 130.7, 127.9, 127.7, 126.9, 126.6, 124.5, 122.9, 122.0, 121.7, 121. 3, 121.2, 119.8, 118.4, 118.2, 116.9, 116.1, 115.9, 114.3, 111.9, 35.6, 35.2, 32.1 (3C), 31.6 (3C); HRMS (ESI) m / z: [M + ]calcd.ForC 30 H 27 NS, 433.1864; found, 433.1855.

[0048] Example 5

[0049] Synthesis of 5,9-di-tert-butylnaphthoindolizine-phenothiazine compounds

[0050] To a 38 mL pressure-resistant reaction flask, 1,9-dibromo-3,7-di-tert-butyl-10-(naphthalen-1-yl)-10H-phenothiazine (0.3 g, 0.51 mmol), palladium acetate (0.02 g, 0.11 mmol), tricyclohexylphosphine tetrafluoroborate (0.08 g, 0.21 mmol), and anhydrous potassium carbonate (0.42 g, 3 mmol) were added in sequence. Under argon, anhydrous dimethylacetamide (3 mL) was added and bubbled continuously for 3 minutes. The mixture was stirred at 160°C for 24 hours. After the reaction, the mixture was cooled to room temperature, and dichloromethane (50 mL) was added. The mixture was washed three times with water, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated to dryness. The crude product was purified by silica gel column chromatography (eluent: n-hexane:dichloromethane = 50 / 1, v / v) to obtain the desired product (0.12 g, yellow solid, 54% yield).

[0051] 1 H NMR (600MHz, CDCl3, 298K) δ8.02 (d, J=9.0Hz, 1H), 7.99 (d, J=7.8Hz, 1H), 7.90 (d, J=7.8Hz, 1H), 7.87 (d, J=1.2Hz, 1H), 7.73 (d, J= 1.2Hz, 1H), 7.68 (t, J=7.8Hz, 1H), 7.58 (d, J=9.0Hz, 1H), 7.16 (d, J=1.2Hz, 1H), 7.06 (d, J=1.2HZ, 1H), 1.45 (s, 9H), 1.42 (s, 9H); 13 C NMR (150MHZ, CDCl3, 298K) δ147.7, 147.4, 132.0, 130.7, 127.9, 127.7, 126.9, 126.6, 124.5, 122.9, 122.0, 121.7, 121. 3, 121.2, 119.8, 118.4, 118.2, 116.9, 116.1, 115.9, 114.3, 111.9, 35.6, 35.2, 32.1 (3C), 31.6 (3C); HRMS (ESI) m / z: [M + ]calcd.ForC 30 H 27 NS, 433.1864; found, 433.1855.

[0052] Example 6

[0053] Synthesis of 5,9-di-tert-butylnaphthoindolizine-phenothiazine compounds

[0054] Into a 38 mL pressure-tight reaction vessel, 1,9-dibromo-3,7-di-tert-butyl-10-(naphthalen-1-yl)-10H-phenothiazine compound (0.4 g, 0.68 mmol), palladium acetate (0.03 g, 0.14 mmol), tricyclohexylphosphonium tetrafluoroborate (0.10 g, 0.28 mmol), anhydrous potassium carbonate (0.56 g, 4 mmol) were added in sequence. Under argon protection, anhydrous dimethylacetamide (4 mL) was added and bubbling was continued for 3 min, and stirring was carried out at 160 °C for 24 h. After the reaction was completed, it was cooled to room temperature, dichloromethane (50 mL) was added, washed with water 3 times, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated and dried. The crude product was separated and purified by silica gel column chromatography (eluent: n-hexane / dichloromethane = 50 / 1, V / V) to obtain the target product (0.16 g, yellow solid, yield 54%).

[0055] 1 H NMR (600 MHz, CDC13, 298 K) δ 8.02 (d, J = 9.0 Hz, 1H), 7.99 (d, J = 7.8 Hz, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.87 (d, J = 1.2 Hz, 1H), 7.73 (d, J = 1.2 Hz, 1H), 7.68 (t, J = 7.8 Hz, 1H), 7.58 (d, J = 9.0 Hz, 1H), 7.16 (d, J = 1.2 Hz, 1H), 7.06 (d, J = 1.2 Hz, 1H), 1.45 (s, 9H), 1.42 (s, 9H); 13 C NMR (150 MHz, CDC13, 298 K) δ 147.7, 147.4, 132.0, 130.7, 127.9, 127.7, 126.9, 126.6, 124.5, 122.9, 122.0, 121.7, 121.3, 121.2, 119.8, 118.4, 118.2, 116.9, 116.1, 115.9, 114.3, 111.9, 35.6, 35.2, 32.1 (3C), 31.6 (3C); HRMS (ESI) m / z: [M + ] calcd. for C 30 H 27 NS, 433.1864; found, 433.1855.

[0056] Example 7

[0057] 5,9-di-tert-butyl naphthoindolizine phenothiazine compound anti-cancer activity experiment on human non-small cell lung cancer cells (A549), human prostate cancer cells (PC-3), human liver cancer cells (HepG2), human cervical cancer cells (Hela), human breast cancer cells (MCF-7), the specific experimental method is as follows:

[0058] The cytotoxicity of 5,9-di-tert-butylnaphthoindole phenothiazine compounds to human non-small cell lung cancer cells (A549), human prostate cancer cells (PC-3), human liver cancer cells (HepG2), human cervical cancer cells (Hela), human breast cancer cells (MCF-7) and normal human umbilical vein endothelial cells (HUVEC) was studied by MTT thiazolyl blue colorimetry. 5 A single cell suspension of 100 μL / mL was inoculated on a 96-well culture plate, with 100 μL per well. After culturing for 24 h in a 37°C incubator with a volume fraction of 5% carbon dioxide and saturated humidity, 100 μL of the sample to be tested at different concentrations was added to the culture plate, with 6 replicates for each concentration. After culturing for 48 h, 100 μL (1 mg / mL) of MTT staining solution was added to each well, and the plate was incubated for another 4 h in the incubator. The supernatant was removed, and then 200 μL of the sample to be tested was added to each well. DMSO was fully shaken for 15 minutes, and the OD sample value was measured at a wavelength of 595 nm on a microplate reader. The blank group of the experiment was 100 μL serum-free DMEM culture medium with DMSO reagent added instead of the sample. The absorbance value at this time was the OD blank value. The inhibition rate of 5,9-di-tert-butylnaphthoindolizine and phenothiazine compounds on A549, PC-3, HepG2, Hela, MCF-7, and HUVEC cells was calculated by formula (1). Finally, the IC 50 .

[0059] m=1-n=1-OD 样 / OD 空白 (1)

[0060] m: inhibition rate n: cell survival rate

[0061] The anticancer activity test results of 5,9-di-tert-butylnaphthoindolizine and phenothiazine compounds against A549, PC-3, HepG2, Hela, and MCF-7 are shown in Table 1:

[0062] Table 1. Cytotoxic activity of 5,9-di-tert-butylnaphthoindolizine and phenothiazine compounds and the control positive drug cisplatin (DDP) against A549, PC-3, HepG2, Hela, MCF-7, and HUVEC (data in the table are IC 50 value):

[0063] Compound A549 PC-3 HepG2 Hela MCF-7 HUVEC This patent 0.21 1.26 6.78 7.99 25.46 26.81 DDP 51.92 14.51 18.91 18.58 39.88 26.48

[0064] As shown in Table 1, the 5,9-di-tert-butylnaphthoindolizine and phenothiazine compound synthesized in this patent exhibited different degrees of inhibitory effects on A549, PC-3, HepG2, Hela, and MCF-7, with significant effects, all of which were superior to the control positive drug cisplatin (DDP). Among them, the inhibitory effect on A549 was particularly prominent, with its IC 50 The value is two orders of magnitude lower than that of cisplatin. Preliminary toxicity experiments show that the compound has low cytotoxicity characteristics, showing good prospects for development as an anti-cancer drug.

Claims

1. A 5,9-di-tert-butylnaphthoindolizine-phenothiazine compound, characterized in that: The structural formula is shown in formula (I):

2. The method for preparing 5,9-di-tert-butylnaphthoindolizine-phenothiazine compound according to claim 1, wherein The following steps are involved: The 1,9-dibromo-3,7-di-tert-butyl-10-(naphthalen-1-yl)-10H-phenothiazine compound represented by formula (II) is used as a raw material, in the presence of palladium acetate, tricyclohexylphosphine tetrafluoroborate, anhydrous potassium carbonate, and anhydrous dimethylacetamide as a solvent, and the reaction is heated at 160°C for 24 hours to obtain the product. Structural formula (II) 3. The method for preparing the 5,9-di-tert-butylnaphthoindolizine-phenothiazine compound according to claim 2, wherein: The preparation of the 1,9-dibromo-3,7-di-tert-butyl-10-(naphthalene-1-yl)-10H-phenothiazine compound represented by formula (II) comprises: using the 1,9-dibromo-3,7-di-tert-butyl-10H-phenothiazine compound represented by formula (III) and 1-iodonaphthalene as raw materials, in the presence of cuprous iodide, 18-crown ether-6, and anhydrous potassium carbonate, using anhydrous 1,2-dichlorobenzene as a solvent, and heating the mixture at 180° C. for 48 hours to obtain the obtained compound; Formula (III) 4. The method for preparing 5,9-di-tert-butylnaphthoindolizine-phenothiazine compound according to claim 2, wherein: The molar ratio of the 1,9-dibromo-3,7-di-tert-butyl-10-(naphthalen-1-yl)-10H-phenothiazine compound, palladium acetate, tricyclohexylphosphine tetrafluoroborate, and anhydrous potassium carbonate is 1:0.2:0.4:

6.

5. Use of the 5,9-di-tert-butylnaphthoindolizinophenothiazine compound according to claim 1 in the preparation of anticancer drugs.

6. Use of the 5,9-di-tert-butylnaphthoindolizin-phenothiazine compound according to claim 5 in the preparation of anticancer drugs, characterized in that: The anticancer drug is used to treat human non-small cell lung cancer (A549).

7. Use of the 5,9-di-tert-butylnaphthoindolizin-phenothiazine compound according to claim 5 in the preparation of anticancer drugs, characterized in that: The anticancer drug is used for treating human prostate cancer (PC-3).

8. Use of the 5,9-di-tert-butylnaphthoindolizin-phenothiazine compound according to claim 5 in the preparation of anticancer drugs, characterized in that: The anticancer drug is used to treat human liver cancer (HepG2).

9. Use of the 5,9-di-tert-butylnaphthoindolizinophenothiazine compound according to claim 5 in the preparation of anticancer drugs, characterized in that: The anticancer drug is used for treating human cervical cancer (Hela).

10. Use of the 5,9-di-tert-butylnaphthoindolizinophenothiazine compound according to claim 5 in the preparation of anticancer drugs, characterized in that: The anticancer drug is used for treating human breast cancer (MCF-7).

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