Chiral spiral double-iron complex as well as preparation method and anti-tumor application thereof

Abstract

The invention discloses an azobenzene chiral spiral double-iron complex as well as a preparation method, a pharmaceutical composition and anti-tumor application thereof, and belongs to the technical field of pharmaceutical chemistry. The synthesis route is short, the structure of the complex is novel, the optically pure enantiomer can be obtained without chiral resolution, and the method has important significance on research and development of chiral metal drugs. Meanwhile, in-vitro anti-tumor activity screening shows that the complex has a relatively strong inhibition effect on the growth of human breast cancer cells, human tongue squamous carcinoma cells and human colon cancer cells, shows obvious enantiomer selectivity, and has a good application prospect and development space of anti-tumor drugs.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical chemistry, and more specifically, relates to a series of azobenzene chiral helical diiron complexes, preparation methods thereof, pharmaceutical compositions and anti-tumor applications thereof. Background Art

[0002] Helical metal complexes with spatial chirality, which are complexed by two or more metal ions and multi-stranded bidentate or tridentate ligands, can simulate the helical structure commonly found in proteins and nucleic acids. They are of great significance for understanding the life process and have attracted widespread attention in the biomedical field (Chem. Sci. 2021, 12, 1620-1631.).

[0003] Studies have shown that helical metal complexes have significant anti-tumor activity. For example, a helical bis-ruthenium complex synthesized from diaminodiphenylmethane, pyridine-2-carboxaldehyde and divalent ruthenium salt has in vitro anti-breast cancer cell HBL-100 activity (Angew. Chem. Int. Ed. 2007, 46, 4374-4378.). A helical bis-ruthenium complex prepared by combining thiazole bipyridine as a tridentate chelating center with divalent ruthenium salt has in vitro anti-colon cancer cell HCT116 p53 activity. - / - activity (Angew.Chem.Int.Ed.2018,57,9799-9804.). The spiral biiridium complex synthesized by pyridinephenyl bidentate ligand and trivalent iridium salt has photodynamic activity, and its activity against breast cancer cells MCF-7 under light conditions is below 1μm (Angew.Chem.Int.Ed.2020,132,6482-6489.). The spiral biiron complex generated by self-assembly of chiral dibenzylamine, pyridine aldehyde and ferrous chloride can induce apoptosis of breast cancer and colon cancer cells (Chem.Sci.2016,7,951-958). The spiral bicobalt complex generated by self-assembly of chiral bipyridine bibenzylamine, pyridine aldehyde and cobaltous chloride can inhibit the aggregation of microtubules in colon cancer cells (Chem.Sci.2024,15,11029-11037). Therefore, it is of great significance to synthesize spiral metal complexes with novel structures.

[0004] The present invention is the first to use azobenzene as a bridge to synthesize chiral diamine ligand precursors, 2-pyridinecarboxaldehyde derivatives and divalent iron salts for self-assembly, prepare a series of novel chiral helical diiron complexes, and develop their application in the anti-tumor field. Summary of the invention

[0005] The purpose of the present invention is to provide a type of chiral helical diiron complexes with novel structure and azobenzene as a bridge.

[0006] Another object of the present invention is to provide a method for preparing the helical diiron complex.

[0007] Another object of the present invention is to provide the use of the helical diiron complex in the preparation of anti-tumor drugs.

[0008] Another object of the present invention is to provide a pharmaceutical composition comprising the above-mentioned helical biferron complex.

[0009] Another object of the present invention is to provide a pharmaceutical preparation comprising the above-mentioned helical biferric complex.

[0010] The above-mentioned purpose of the present invention is achieved through the following technical solutions:

[0011] The present invention relates to a material having the general formula Δ-[Fe2L n 3]Cl4 and Λ-[Fe2L n 3] a helical diiron complex of Cl4, the structural formula of the complex is as follows:

[0012]

[0013] Wherein R is selected from hydrogen, C 1-6 Alkoxy, C 3-6 Alkynyloxy, glycosyl, unsubstituted or optionally substituted with one, two or more C 1-6 Alkyl, C 1-6 One of an alkoxy group, a cyano group or a halogen-substituted benzyloxy group.

[0014] According to the present invention, preferred complexes include:

[0015]

[0016] In some embodiments of the present invention, the present invention also relates to a pharmaceutical composition containing a pharmaceutically effective amount of a general formula Δ-[Fe2L n 3]Cl4 and Λ-[Fe2L n 3] A pharmaceutical composition of the complex described in C14 and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier is selected from: a binder, a filler, a diluent, a disintegrant, a suspending agent, a suspending aid, a sustained (controlled) release agent, a lyophilization protectant, a coating agent, an enteric material, a lubricant, a glidant, an anti-adherent, a sweetener, a flavoring agent, a plasticizer, a sunscreen, a solubilizer, a humectant, a solvent, an osmotic pressure regulator, a colorant, a pigment, a surfactant, an emulsifier, a water-soluble matrix, a fat-soluble matrix, an oil-soluble matrix, a pore-forming agent, a gelling agent, a preservative, a buffer, a chelating agent, an antioxidant, or a combination thereof.

[0017] In some embodiments of the present invention, the complex of the present invention or the pharmaceutical composition containing it can be administered in a unit dosage form, and the administration route can be enteral or parenteral, such as oral, intravenous, intramuscular, subcutaneous, nasal, oral mucosa, eyes, lungs and respiratory tract, skin, vagina, rectum, etc.

[0018] Another aspect of the present invention is to combine the complex of the present invention with one or more pharmaceutically acceptable carriers to prepare a dosage form suitable for human or animal use, which can be a liquid dosage form, a solid dosage form or a semisolid dosage form. The liquid dosage form can be a solution (including a true solution and a colloidal solution), an emulsion (including an o / w type, a w / o type and a multiple emulsion), a suspension, an injection (including a water injection, a powder injection and an infusion), an eye drop, a nasal drop, a lotion and an liniment, etc.; the solid dosage form can be a tablet (including a common tablet, an enteric-coated tablet, a lozenge, a dispersible tablet, a chewable tablet, an effervescent tablet, an orally disintegrating tablet), a capsule (including a hard capsule, a soft capsule, an enteric-coated capsule), a granule, a powder, a micropill, a dropping pill, a suppository, a film, a patch, an aerosol (powder) spray, a spray, etc.; the semisolid dosage form can be an ointment, a gel, a paste, etc.

[0019] In some embodiments of the present invention, the complex of the present invention or the pharmaceutical composition containing the complex can be prepared into common preparations, sustained-release preparations, controlled-release preparations, targeted preparations and various microparticle drug delivery systems.

[0020] In some embodiments of the present invention, the complex of the present invention or the pharmaceutical composition containing the complex can be taken alone or used in combination with other therapeutic drugs or symptomatic drugs.

[0021] Another aspect of the present invention provides a method for preparing the helical diiron complex, comprising the following steps:

[0022] (1) 4,4'-Bis(bromomethyl)azobenzene is used as a starting material and reacted with R-phenylglycinol or S-phenylglycinol under heating and reflux to obtain the intermediate material (R,R)-2 or (S,S)-2; 5-hydroxy-2-pyridinecarboxaldehyde is used as a starting material and reacted with different brominated materials under heating and reflux to obtain the intermediate material 2-pyridinecarboxaldehyde derivative 3.

[0023] (2) The intermediate raw material (R,R)-2 or (S,S)-2, 2-pyridinecarboxaldehyde derivative 3 and divalent iron salt are reacted under heating reflux to obtain the target product Δ-[Fe2L n 3]Cl4 or Λ-[Fe2L n 3]Cl4.

[0024] The preparation method according to a preferred embodiment of the present invention has at least the following beneficial effects: the preparation process of the present invention is simple, easy to operate, and has good industrial application prospects.

[0025] According to another aspect of the present invention, the use of the above-mentioned helical diiron complex in anti-tumor treatment is proposed.

[0026] In some preferred embodiments of the present invention, the tumor is a solid tumor such as breast cancer, tongue squamous cell carcinoma or colon cancer.

[0027] Other features and advantages of the present invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learned by practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0029] Figure 1 In Example 1, the complex Δ-[Fe2L 1 3]Cl4 1 H NMR spectrum.

[0030] Figure 2 In Example 13, the complex Δ-[Fe2L 1 3]Cl4 and its enantiomer Λ-[Fe2L 1 3] Circular dichroism spectrum of Cl4 in methanol solution. DETAILED DESCRIPTION

[0031] The following will clearly and completely describe the concept of the present invention and the technical effects produced in combination with the embodiments, so as to fully understand the purpose, characteristics and effects of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, other embodiments obtained by technicians in this field without creative work are all within the scope of protection of the present invention. The test methods used in the embodiments are all conventional methods unless otherwise specified; the materials, reagents, etc. used, unless otherwise specified, can all be reagents and materials obtained from commercial channels.

[0032] Synthesis method of the compound:

[0033] (1) Preparation of intermediate raw materials (R,R)-2, (S,S)-2 and 2-pyridinecarboxaldehyde derivative 3

[0034] Preparation of (R,R)-2 and (S,S)-2: R-phenylglycinol or S-phenylglycinol (11.96 mmol, 2.3 eq) was dissolved in 100 ml of anhydrous tetrahydrofuran, and stirred at room temperature until completely dissolved. Then, 4,4'-di(bromomethyl)azobenzene (5.20 mmol, 1 eq) and NaH (24.00 mmol, 4.6 eq) were slowly added. After stirring at room temperature for 1 h, the mixture was heated to 65°C and continued to stir for 6 h. The crude product was purified by silica gel column chromatography (eluent: dichloromethane: petroleum ether: methanol = 20:4:1), and dried in vacuo to obtain the intermediate raw material (R,R)-2 or (S,S)-2.

[0035] The chemical reaction equations involved are shown below:

[0036]

[0037] Preparation of 2-pyridinecarboxaldehyde derivative 3: 2-pyridinecarboxaldehyde derivative 3a is a commercially available raw material pyridine-2-carboxaldehyde. Preparation of 2-pyridinecarboxaldehyde derivatives 3b, 3c, 3d, 3e and 3f: 5-hydroxy-2-pyridinecarboxaldehyde is used as the starting material and prepared according to reference (Chem. Sci. 2019, 10 (37), 8547-8557.). The structural formula of the 2-pyridinecarboxaldehyde derivative 3 involved in the preferred embodiment is as follows:

[0038]

[0039] (2) Preparation of final product

[0040] The intermediate raw material (R,R)-2 or (S,S)-2 (0.11mmol, 3eq) and 2-pyridinecarboxaldehyde derivative 3 (0.21mmol, 6eq) were dissolved in 15mL of anhydrous methanol and stirred at room temperature for 30min until completely dissolved. Anhydrous FeCl2 (0.07mmol, 2eq) was added and stirred at 70℃ for 48h. The crude product was filtered, purified by recrystallization and vacuum dried to obtain the target product Δ-[Fe2L n 3]Cl4 or Λ-[Fe2L n 3]Cl4.

[0041] The chemical reaction equation involved in step (2) is as follows:

[0042]

[0043] Example 1 Complex Δ-[Fe2L 1 3] Preparation of Cl4

[0044]

[0045] The intermediate raw materials (R,R)-2 (0.11mmol, 3eq) and intermediate raw materials 3a (0.21mmol, 6eq) were dissolved in 15mL of anhydrous methanol and stirred at room temperature for 30min until completely dissolved. Anhydrous FeCl2 (0.07mmol, 2eq) was added and stirred at 70℃ for 48h. The crude product was filtered, purified by recrystallization and vacuum dried to obtain the target product Δ-[Fe2L 1 3]Cl4. Yield: 85.45%. 1 H-NMR (800MHz, CD3OD): 9.30 (s, 6H), 7.82 (t, J = 7.7Hz, 6H), 7.78 (d, J = 7.8Hz, 12H), 7. 58(d,J=7.6Hz,6H), 7.48(d,J=7.8Hz,12H), 7.30(t,J=6.6Hz,6H,), 7.16(t,J=7.4Hz,1 H), 7.08(t,J=7.5Hz,12H), 6.89(d,J=7.2Hz,12H), 6.85(d,J=5.3Hz,6H), 5.92(d,J=8. 5Hz, 6H), 4.90 (d, J = 12.3Hz, 6H), 4.51 (dd, J = 26.8, 11.8Hz, 2H), 3.75 (d, J = 9.3Hz, 1H). HRMS:Calculated for[Fe2L3]Cl 3+ m / z 707.5858, found m / z 707.6026; [Fe2L3] 4+ m / z 521.9470, foundm / z 521.9565.

[0046] Example 2 Complex Λ-[Fe2L 1 3] Preparation of Cl4

[0047]

[0048] The preparation method of this embodiment can refer to that of embodiment 2, except that the intermediate raw material (S,S)-2 is replaced by (R,R)-2. Yield: 85.21%. 1 H-NMR and HRMS data are consistent with those of Δ-[Fe2L 1 3]Cl4 data are consistent.

[0049] Example 3 Complex Δ-[Fe2L 2 3] Preparation of Cl4

[0050]

[0051] The preparation method of this embodiment can refer to that of embodiment 1, except that the intermediate raw material 3a is replaced by 3b. Yield: 85.26%. 1 H-NMR (800MHz, CD3OD): 9.05 (s, 6H), 7.73 (d, J = 7.7Hz, 12H), 7.42 (t, J = 10.4Hz, 24H), 7. 35(t,J=8.7Hz,18H),7.22(d,J=7.1Hz,12H),7.09(t,J=7.6Hz,6H),6.98(t,J=7.5Hz,12H ),6.77(d,J=7.6Hz,12H),6.31(s,6H),5.70(d,J=10.6Hz,6H),5.17–5.03(m,12H),4.82( d, J=12.3Hz, 6H), 4.46 (d, J=12.3Hz, 6H), 4.38 (t, J=11.4Hz, 6H), 3.64 (d, J=11.4Hz, 6H).

[0052] Example 4 Complex Λ-[Fe2L 2 3] Preparation of Cl4

[0053]

[0054] The preparation method of this embodiment can refer to that of embodiment 1, except that the intermediate raw material (S,S)-2 is replaced by (R,R)-2, and the intermediate raw material 3a is replaced by 3b. Yield: 83.35%. 1 H-NMR data are similar to those of Δ-[Fe2L 2 3]Cl4 data are consistent.

[0055] Example 5 Complex Δ-[Fe2L 3 3] Preparation of Cl4

[0056]

[0057] The preparation method of this embodiment can refer to that of embodiment 1, except that the intermediate raw material 3a is replaced by 3c. Yield: 84.22%. 1H-NMR (800MHz, CD3OD): 9.11 (s, 6H), 7.74 (d, J = 7.6Hz, 12H), 7.49 (s, 6H), 7.43 (t, J=8.6Hz,18H),7.32(d,J=7.0Hz,12H),7.11(q,J=9.0Hz,18H),7.01(t,J=7.5Hz,1 2H),6.83(d,J=7.2Hz,12H),6.34(s,6H),5.73(d,J=10.2Hz,6H),5.08(s,12H),4. 83 (s, 6H), 4.48 (d, J = 12.0Hz, 6H), 4.41 (t, J = 10.9Hz, 6H), 3.66 (d, J = 10.9Hz, 6H).

[0058] Example 6 Complex Λ-[Fe2L 3 3] Preparation of Cl4

[0059]

[0060] The preparation method of this example can refer to Example 1, except that the intermediate raw material (S, S)-2 is replaced by (R, R)-2, and the intermediate raw material 3a is replaced by 3c. Yield: 82.98%. 1 H-NMR data are similar to those of Δ-[Fe2L 3 3]Cl4 data are consistent.

[0061] Example 7 Complex Δ-[Fe2L 4 3] Preparation of Cl4

[0062]

[0063] The preparation method of this embodiment can refer to that of embodiment 1, except that the intermediate raw material 3a is replaced by 3d. Yield: 82.75%. 1 H-NMR (800MHz, CD3OD): 9.14 (s, 6H), 7.74 (t, J = 7.4Hz, 30H), 7.52–7.48 (m, 18H), 7 .46(d,J=9.5Hz,6H),7.43(d,J=7.9Hz,12H),7.14(t,J=7.6Hz,6H),7.05(t,J=7.5 Hz,12H),6.86(d,J=7.6Hz,12H),6.41(s,6H),5.75(d,J=10.5Hz,6H),5.22(q,J=1 3.0Hz, 12H), 4.49 (d, J = 12.3Hz, 6H), 4.42 (t, J = 9.4Hz, 6H), 3.67 (d, J = 11.4Hz, 6H).

[0064] Example 8 Complex Λ-[Fe2L 4 3] Preparation of Cl4

[0065]

[0066] The preparation method of this example can refer to Example 1, except that the intermediate raw material (S, S)-2 is replaced by (R, R)-2, and the intermediate raw material 3a is replaced by 3d. Yield: 83.77%. 1 H-NMR data are similar to those of Δ-[Fe2L 4 3]Cl4 data are consistent.

[0067] Example 9 Complex Δ-[Fe2L 5 3] Preparation of Cl4

[0068]

[0069] The preparation method of this embodiment can refer to that of embodiment 1, except that the intermediate raw material 3a is replaced by 3e. Yield: 83.17%. 1 H-NMR (800MHz, CD3OD): 9.21 (s, 6H), 7.77 (d, J = 7.7Hz, 12H), 7.57 (d, J = 8.6Hz, 6H), 7.46(d,J=8.1Hz,18H),7.42(d,J=8.6Hz,12H),7.18(t,J=7.4Hz,6H),7.13(d,J=7. 8Hz,12H),6.93(d,J=7.7Hz,12H),6.53(s,6H),5.83(d,J=10.8Hz,6H),4.74(q,J=1 6.8Hz, 18H), 4.52 (d, J = 12.2Hz, 6H), 4.47 (t, J = 11.3Hz, 6H), 3.72 (d, J = 11.5Hz, 6H).

[0070] Example 10 Complex Λ-[Fe2L 5 3] Preparation of Cl4

[0071]

[0072] The preparation method of this example can refer to Example 1, except that the intermediate raw material (S, S)-2 is replaced by (R, R)-2, and the intermediate raw material 3a is replaced by 3e. Yield: 81.20%. 1 H-NMR data are similar to those of Δ-[Fe2L 5 3]Cl4 data are consistent.

[0073] Example 11 Complex Δ-[Fe2L 6 3] Preparation of Cl4

[0074]

[0075] The preparation method of this example can refer to Example 1, except that the intermediate raw material 3a is replaced by 3f. Yield: 79.95%. 1 H-NMR (800MHz, CD3OD): 9.21 (s, 6H), 7.77 (d, J = 7.7Hz, 12H), 7.57 (d, J = 8.6Hz, 6H), 7. 46(d,J=8.1Hz,12H),7.42(d,J=8.6Hz,6H),7.18(t,J=7.4Hz,6H),7.13(d,J=7.8Hz,12 H),6.93(d,J=7.7Hz,12H),6.53(s,6H),5.83(d,J=10.8Hz,6H),4.74(q,J=16.8Hz,12H ), 4.52 (d, J = 12.2Hz, 6H), 4.47 (t, J = 11.3Hz, 6H), 3.72 (d, J = 11.5Hz, 6H), 3.22 (s, 6H).

[0076] Example 12 Complex Λ-[Fe2L 6 3] Preparation of Cl4

[0077]

[0078] The preparation method of this example can refer to Example 1, except that the intermediate raw material (S, S)-2 is replaced by (R, R)-2, and the intermediate raw material 3a is replaced by 3f. Yield: 78.51%. 1 H-NMR data are similar to those of Δ-[Fe2L 6 3]Cl4 data are consistent.

[0079] Example 13 Application Example: Complex Δ-[Fe2L 1 3]Cl4 and its enantiomer Λ-[Fe2L 1 3] Circular dichroism detection of Cl4

[0080] (1) Experimental method: At room temperature, Δ-[Fe2L 1 3]Cl4 and Λ-[Fe2L 1 3]Cl4 was prepared into 1.5×10 -5 mol / L concentration of methanol solution, and test the circular dichroism spectra of both.

[0081] (2) Experimental results: Due to Δ-[Fe2L1 3]Cl4 and Λ-[Fe2L 1 3]Cl4 are enantiomers, and their circular dichroism spectra are mirror-symmetrical.

[0082] Example 14 Application Example: Complex Δ-[Fe2L 1-6 3]Cl4 and Λ-[Fe2L 1-6 Detection of antitumor activity of 3]Cl4

[0083] (1) Experimental method: The MTT colorimetric method was used. The cells were collected by trypsin digestion and resuspended in culture medium into a single cell suspension. The cell concentration was adjusted to 3×10 4 / mL, inoculated in 96-well plates, 100 μL per well, cultured for 24 h, and then added 25 μL of gradient concentrations of drugs (Δ-[Fe2L 1-6 3]Cl4, Λ-[Fe2L 1-6 3]Cl4 or cisplatin), placed in an incubator containing 5% CO2, incubated at 37°C for 72h, and added 25μL / well of MTT solution with a concentration of 5mg / mL 4h before the end of incubation. After incubation in the incubator for 4h, the supernatant was discarded, 100μL of DMSO solution was added to each well, and the OD value was measured with an enzyme marker after oscillation for 15min, with the wavelength set to 490nm. The tested cell lines were MDA-MB-231 (human breast cancer cell line), CAL-27 (human tongue squamous cell carcinoma cell line), and HCT116 (human colon cancer cell line).

[0084] (2) Experimental results: Calculate the survival rate of the tested tumor cells, plot and calculate the IC 50 The anti-tumor activity of the complex was evaluated and the results are shown in Table 1.

[0085] Table 1 Evaluation of the antitumor activity of the synthesized helical diiron complexes

[0086]

[0087] The experimental results showed that most of the complexes showed strong in vitro antitumor activity, among which Λ-[Fe2L 1 Effect of 3]Cl4 on CAL-27, HCT116 cell lines and Λ-[Fe2L 5 IC of 3]Cl4 on CAL-27 cell line 50 All of them were less than 1 μM. In addition, the anti-tumor activity of Λ-configuration complexes was generally better than that of Δ-configuration complexes.

[0088] In summary, the present invention provides a novel chiral helical diiron complex with anti-tumor activity, a preparation method thereof and anti-tumor application thereof. The complex synthesized by the present invention has a good effect of inhibiting tumor cell proliferation, and the anti-tumor effect of some complexes is better than that of cisplatin, and shows obvious enantiomeric selectivity, which is worthy of further study and is expected to be developed into a new anti-tumor drug.

[0089] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit it. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present application.

Claims

1. With the general formula of Δ-[Fe2L n 3]Cl4 and Λ-[Fe2L n 3] A helical diiron complex of Cl4 or a pharmaceutically acceptable salt thereof, characterized in that: Including the following structure:

2. The helical biferric complex or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: R is selected from hydrogen, C 1-6 Alkoxy, C 3-6 Alkynyloxy, glycosyl, unsubstituted or optionally substituted with one, two or more C 1-6 Alkyl, C 1-6 Alkoxy, cyano or halogen-substituted benzyloxy. Preferably, R is selected from hydrogen, propynyloxy, benzyloxy, 4-fluorobenzyloxy, 4-cyanobenzyloxy or β-D-glucosyl.

3. The helical biferric complex or a pharmaceutically acceptable salt thereof according to claim 1-2, characterized in that: The compound is selected from:

4. The method for preparing the helical diiron complex according to claims 1-3, characterized in that: The steps include: (1) reacting 4,4'-bis(bromomethyl)azobenzene with R-phenylglycinol or S-phenylglycinol under heating and reflux to obtain an intermediate raw material (R,R)-2 or (S,S)-2; (2) The intermediate raw material (R,R)-2 or (S,S)-2, 2-pyridinecarboxaldehyde derivative 3 and anhydrous FeCl2 are reacted under heating reflux to obtain the target product Δ-[Fe2L n 3]X4 or Λ-[Fe2L n 3]X4.

5. The preparation method according to claim 4, characterized in that: The specific process of step (1) is as follows: R-phenylglycine alcohol or S-phenylglycine alcohol is dissolved in anhydrous tetrahydrofuran, and after complete dissolution, 4,4'-di(bromomethyl)azobenzene and NaH are added, stirred at room temperature for 1 hour, heated to 65° C. and continued to stir for 6 hours. The obtained crude product is purified by silica gel column chromatography and vacuum dried to obtain the intermediate raw material (R,R)-2 or (S,S)-2.

6. The preparation method according to claim 4, characterized in that: The specific process of step (2) is as follows: the intermediate raw material (R,R)-2 or (S,S)-2, 2-pyridine carboxaldehyde derivative 3 is dissolved in anhydrous methanol, stirred at room temperature for 30 minutes until completely dissolved, anhydrous FeCl2 is added, heated and stirred at 70°C for 48 hours, the crude product is filtered, purified by recrystallization, and vacuum dried to obtain the target product Δ-[Fe2L n 3]X4 or Λ-[Fe2L n 3]X4.

7. A pharmaceutical composition, characterized in that The pharmaceutical composition comprises the helical biferron complex or a pharmaceutically acceptable salt thereof according to claims 1-3; preferably, the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients.

8. The pharmaceutical composition according to claim 7, characterized in that The dosage form of the pharmaceutical composition is selected from tablets, capsules, pills, injections, sustained-release preparations, controlled-release preparations or various microparticle delivery systems.

9. Use of the complex according to any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 7 or 8 in the preparation of anti-tumor drugs.

10. The use according to claim 9, characterized in that: The tumor is a solid tumor such as breast cancer, tongue squamous cell carcinoma or colon cancer. Preferably, the breast cancer is MDA-MB-231 cell line breast cancer, the tongue squamous cell carcinoma is CAL-27 cell line tongue squamous cell carcinoma, and the colon cancer is HCT116 cell line colon cancer.

Images