Cationic pyrrole compound with aggregation-induced emission property as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of medicines, and discloses a cationic pyrrole compound with an aggregation-induced emission property as well as a preparation method and application thereof. The structure of the cationic pyrrole compound is shown as a formula I or a formula IV. The invention discloses a preparation method of the compound. The compound can specifically target mitochondria, is combined with SDHAF1 protein with high affinity, and inhibits the activity and oxidative phosphorylation function of a compound II, thereby efficiently killing acute myelogenous leukemia cells. Meanwhile, the compound also shows remarkable inhibitory activity on pathogenic fungi such as candida albicans. The compound provided by the invention is used for preparing SDHAF1 inhibitors, mitochondrial targeting fluorescence imaging agents, drugs for treating oxidative phosphorylation dependent cancers such as acute myelogenous leukemia and / or antifungal drugs. Formula I: Formula IV:

Description

A class of cationic pyrrole compounds with aggregation-induced emission properties, their preparation methods and applications Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a class of cationic pyrrole compounds with aggregation-induced emission properties, their preparation methods, and the application of such compounds as inhibitors of mitochondrial succinate dehydrogenase assembly factor 1 (SDHAF1) in the preparation of drugs for treating oxidative phosphorylation-dependent cancers such as acute myeloid leukemia (AML), and / or their application as antifungal drugs. Background Technology

[0002] For AML, drug-resistant AML cells rely on mitochondrial oxidative phosphorylation (OXPHOS) for energy. SDHAF1, a key assembly factor of complex II (succinate dehydrogenase, SDH), is an ideal target, but highly selective inhibitors are lacking. Existing OXPHOS inhibitors (such as mubritinib) have poor mitochondrial targeting, while some mitochondrial-targeting fluorescent dyes (such as DiOC5(3)) exhibit aggregation-induced quenching (ACQ) effects, making it impossible to integrate fluorescence imaging with mitochondrial targeting and inhibitory effects.

[0003] For fungal infections, particularly those caused by pathogenic fungi such as Candida, there is an urgent need for drugs with specific mechanisms of action. Mitochondrial function is crucial for fungal survival, but antifungal drugs that directly target SDHAF1 in fungal mitochondria have not yet been reported.

[0004] Therefore, it is of great significance to develop a compound platform that can simultaneously overcome the ACQ effect, specifically target mitochondrial SDHAF1, and possess both highly efficient anticancer and antifungal activities. Summary of the Invention

[0005] To overcome the shortcomings and deficiencies of existing technologies, the present invention aims to provide a cationic pyrrole compound with aggregation-induced emission (AIE) properties, its preparation method, and its applications. The cationic pyrrole compound of the present invention is used as a mitochondrial-targeted SDHAF1 inhibitor, a fluorescent imaging agent, and an antitumor drug. The compound of the present invention can specifically accumulate and bind to SDHAF1 protein in mitochondria, disrupting oxidative phosphorylation (OXPHOS) by inhibiting succinate dehydrogenase (complex II) activity, thereby efficiently killing various tumor cells such as pancreatic cancer cells, breast cancer cells, and acute myeloid leukemia cells. Simultaneously, its inherent AIE properties allow for real-time, in-situ fluorescence imaging of the drug accumulation process and mitochondrial dysfunction, achieving synchronization of drug action and monitoring.

[0006] The cationic pyrrole compounds are used to prepare drugs for the prevention and / or treatment of acute myeloid leukemia (AML). The compounds of this invention specifically kill AML cells by targeting and inhibiting mitochondrial SDHAF1, inhibiting OXPHOS, and inducing mitochondrial dysfunction and apoptosis, and demonstrate significant in vivo therapeutic efficacy and good safety in AML animal models.

[0007] In addition, the cationic pyrrole compounds are also used in the preparation of drugs for treating fungal infections. The compounds of the present invention can target the mitochondria of pathogenic fungi, interfering with their energy metabolism, thereby inhibiting fungal growth.

[0008] The objective of this invention is achieved through the following technical solution:

[0009] A method for preparing a cationic pyrrole compound with aggregation-induced emission properties includes the following steps: oxidizing a compound of formula II to obtain a cationic pyrrole compound of formula I; or mixing and reacting a compound of formula III, an oxidant, and a nucleophile to obtain a cationic pyrrole compound of formula IV.

[0010] Compound II is Compound III is

[0011]

[0012] Formula II Formula III

[0013] In Equation II, R 1 R 2 R 5 For independent hydrogen, halogen, alkyl, alkylene-R' (R' is alkynyl, aryl), alkyloxy (alkyl-O-), alkylcarbonyl (alkyl-C(O)-), alkylthio (alkyl-S-), aryl, cyano, nitro, The aryl group is phenyl, hydroxylated phenyl, methoxylated phenyl, amino-substituted phenyl, or ester-substituted phenyl.

[0014] In Equation II, R 3 R 4 It is hydrogen;

[0015] In Formula III, R 1 R 2 R 5 For independent hydrogen, halogen, alkyl, alkylene-R' (R' is alkynyl, aryl), alkyloxy (alkyl-O-), alkylcarbonyl (alkyl-C(O)-), alkylthio (alkyl-S-), aryl, cyano, nitro, The aryl group is phenyl, hydroxylated phenyl, methoxylated phenyl, amino-substituted phenyl, or ester-substituted phenyl.

[0016] In Formula III, R 4 It is hydrogen.

[0017] In formulas II and III, the alkyl group is preferably C. 1~6 Alkyl groups, such as methyl, ethyl, propyl, butyl, pentyl, and hexyl.

[0018] In alkylene-R', the alkylene group is methylene or ethylene; in R', the aryl group is phenyl, and the alkynyl group is ethynyl, propynyl, etc.

[0019] Preferably, R in Formula II and Formula III 2 R 5 Each is an aryl group, such as phenyl;

[0020] Preferably, R in Formula II and Formula III 1 Alkyl, ethynylmethylene, ethynylethyl, benzyl .

[0021] Preferably, the nucleophile is indole, N-methylindole, N-phenylindole, naphthalene, anthracene, etc.

[0022] In the oxidation of compound II, the oxidation refers to oxidation using an oxidizing agent; the oxidizing agent is copper perchlorate, ferric chloride, or silver hexafluoroantimonate.

[0023] The oxidation is carried out in a solvent.

[0024] When the oxidant is copper perchlorate, silver hexafluoroantimonate, or ferric chloride, the oxidation is carried out using an organic solvent as the reaction medium. The organic solvent is one or more of acetonitrile, dichloromethane, and methanol.

[0025] When the oxidant is copper perchlorate, the organic solvent is preferably acetonitrile; when the oxidant is silver hexafluoroantimonate, the organic solvent is preferably dichloromethane; when the oxidant is ferric chloride, the organic solvent is preferably methanol.

[0026] In the mixed reaction, the oxidant is copper perchlorate or silver hexafluoroantimonate.

[0027] In the mixed reaction, an organic solvent is used as the reaction medium. The organic solvent is one or more of acetonitrile, dichloromethane, and methanol.

[0028] When the oxidant is copper perchlorate, the organic solvent is preferably acetonitrile; when the oxidant is silver hexafluoroantimonate, the organic solvent is preferably dichloromethane.

[0029] Compound III is prepared by the following method: Compound II is oxidized using ferric chloride as an oxidant to obtain Compound III. The oxidation is carried out in an organic solvent, wherein the organic solvent is one or more of dichloromethane and MeNO2. Specifically, Compound II is dissolved in an organic solvent, a MeNO2 solution of ferric chloride is added, and the oxidation reaction is carried out to obtain Compound III. The reaction is carried out at room temperature for 3-4 hours. The molar ratio of Compound II to ferric chloride is 1:(1.5-2.0).

[0030] In the preparation of cationic pyrrole compounds, the oxidation temperature is 20~30 °C, preferably room temperature.

[0031] The oxidation time is 0.2 to 8 hours.

[0032] The molar ratio of the compound of formula II to the oxidant is 1: (0.9~1.2), preferably 1:1.

[0033] The molar ratio of the compound of formula III to the nucleophile and the oxidant is 1:(0.9~1.2):(0.9~1.2), preferably 1:1:1.

[0034] After the oxidation reaction of compound II is complete, it is concentrated under reduced pressure, extracted (by DCM / H2O), and separated and purified by column chromatography. The eluent is dichloromethane / methanol in a volume ratio of (80~95):(5~20), with a total volume fraction of 100 parts for dichloromethane and 80~95 parts for dichloromethane.

[0035] After the compound of Formula III reacts with the oxidant and nucleophile, it is concentrated under reduced pressure, extracted (by DCM / H2O), and purified by column chromatography using ethyl acetate as the eluent.

[0036] The structures of the cationic pyrrole compounds with aggregation-induced emission properties are Formula I and Formula IV, respectively.

[0037]

[0038] Formula I Formula IV

[0039] In Equation I, R 1 ~R 5 As defined in Formula II. Preferably, the R 2 R 5 Each is an aryl group, such as phenyl; R 3 R 4 It is hydrogen;

[0040] The R 1 Alkyl, ethynylmethylene, ethynylethyl, benzyl Y represents the anionic group corresponding to the oxidizing agent, such as ClO4.- SbF6 - Cl - .

[0041] In Equation IV, R 1 ~R 5 As defined in Formula III, R is the group corresponding to the nucleophile after losing a hydrogen atom; Y in Formula I or Formula IV is the anionic group corresponding to the oxidizing agent, such as ClO4 in each case. - SbF6 - Cl - .

[0042] The cationic pyrrole compounds of the present invention, which have aggregation-induced emission properties, are used to prepare SDHAF1 inhibitors, mitochondrial-specific fluorescent imaging agents, and antifungal agents.

[0043] A mitochondrial succinate dehydrogenase assembly factor 1 (SDHAF1) inhibitor comprising a cationic pyrrole compound with aggregation-induced luminescence properties; the structure of which is of formula I and / or formula IV.

[0044]

[0045] Formula I Formula IV

[0046] In Equation I, R 1 ~R 5 As defined in Equation II; when defined in Equation IV, R 1 ~R 5 As defined in Formula III; R is the group corresponding to the nucleophile after losing a hydrogen atom; Y is the anionic group corresponding to the oxidizing agent.

[0047] Preferably, the R described in Formula I 2 R 5 Each is an aryl group, such as phenyl; R 3 R 4 It is hydrogen;

[0048] The R 1 Alkyl, ethynylmethylene, ethynylethyl, benzyl Y represents the anionic group corresponding to the oxidizing agent, such as ClO4. - SbF6 - Cl - .

[0049] Preferably, in formula IV, the R 2 R 5 Each is an aryl group, such as phenyl; R 4 R is hydrogen; R is the group corresponding to the nucleophile after losing a hydrogen atom; Y is the anionic group corresponding to the oxidant.

[0050] The inhibitor is used in the preparation of antitumor drugs, particularly in drugs for treating oxidative phosphorylation-dependent cancers such as acute myeloid leukemia (AML).

[0051] The antitumor drug is prepared as a complex by combining the aforementioned cationic pyrrole compound with aggregation-induced emission properties with a functionalized carrier through a nano-assembly process; wherein the functionalized carrier includes the amphiphilic polymer DSPE-PEG-COOH, and the complex is in the form of nanoparticles. The surface of the complex is modified with L-phenylalanine.

[0052] The use of the inhibitor in the preparation of antifungal drugs.

[0053] A fluorescent imaging agent for mitochondrial-specific fluorescence imaging, comprising a cationic pyrrole compound with aggregation-induced emission properties; having a structural formula of formula I and / or formula IV.

[0054]

[0055] Formula I Formula IV

[0056] In Equation I, R 1 ~R 5 As defined in Equation II; when defined in Equation IV, R 1 ~R 5 As defined in Formula III, R loses a group corresponding to an H with the nucleophile. Specifically, R can be indole, N-methylindole, N-phenylindole, naphthyl, anthracene, etc.

[0057] An agent that specifically targets mitochondrial fluorescence imaging and binds to SDHAF1 protein with high affinity and inhibits the activity of mitochondrial complex II includes a cationic pyrrole compound with aggregation-induced luminescence properties.

[0058] An antifungal drug comprising the above-mentioned cationic pyrrole compound having aggregation-induced emission properties.

[0059] The cationic pyrrole compound with aggregation-induced emission (AIE) properties enables in-situ, real-time fluorescence monitoring during leukemia and fungal infection processes.

[0060] The cationic pyrrole compound of the present invention, which has aggregation-induced emission (AIE) properties, possesses excellent mitochondrial-targeted fluorescence imaging performance, high affinity binding ability to SDHAF1 protein, significant anticancer and antifungal activities, and real-time visualization of the action process.

[0061] The present invention has the following advantages and effects compared with the prior art:

[0062] 1. This invention successfully prepared a cationic pyrrole compound. The preparation method of this cationic pyrrole compound is simple and it is easy to modify various functional groups.

[0063] 2. The cationic pyrrole compound of the present invention can serve as a small molecule inhibitor of the SDHAF1 protein, a target crucial in OXPHOS-dependent cancers such as acute myeloid leukemia, but no targeted drugs have been reported to date. The present invention not only provides a lead compound but also elucidates a clear antitumor mechanism by inhibiting complex II activity and disrupting mitochondrial function.

[0064] 3. The cationic pyrrole compounds of the present invention exhibit significant inhibitory activity against acute myeloid leukemia cells and pathogenic fungi such as Candida albicans, breaking through the limitation of existing drugs that usually target a single pathogen, and providing the possibility for developing drugs that can simultaneously treat malignant tumors and secondary / complication fungal infections. Attached Figure Description

[0065] Figure 1 shows the NMR characterization of compound I-1 in CD2Cl2; Figure 2 shows the NMR characterization of compound I-2 in CD2Cl2; Figure 3 shows the NMR characterization of compound IV-1 in CD2Cl2; Figure 4 shows the NMR characterization of compound IV-2 in CD2Cl2.

[0066] Figure 5 shows the high-resolution mass spectrum of compound I-1; Figure 6 shows the high-resolution mass spectrum of compound I-2; Figure 7 shows the high-resolution mass spectrum of compound IV-1; Figure 8 shows the high-resolution mass spectrum of compound IV-2.

[0067] Figure 9 shows the single crystal structure of compound formula I-1; Figure 10 shows the single crystal structure of compound formula I-2;

[0068] Figure 11 shows the normalized absorption and emission spectra of formulas I-1 to I-3 and formulas IV-1 to IV-2 in dimethyl sulfoxide (50 μM), λ ex = 465 nm;

[0069] Figure 12 shows the emission spectra of Equation I-1 in DMSO / H2O (a, d), DMSO / toluene (b, e), and glycerol-ethanol (c, f) mixtures, with the volume fractions of water, toluene, and glycerol increasing from 10% to 99% (50 μM). ex = 465 nm;

[0070] Figure 13 shows the IC50 values ​​of PaTu-8988t, MCF-7, and THP-1 cells after treatment with compounds I-1 to I-3 for 24 hours. 50 curve;

[0071] Figure 14 shows the cytotoxicity, subcellular imaging, and cytotoxic mechanism of Formula I-1 targeting mitochondria; (a) cell viability of PaTu-8988t, MCF-7, and THP-1 cells after treatment with Formula I-1 for 24 hours; (b) CLSM images of PaTu-8988t, MCF-7, and THP-1 cells co-incubated with Formula I-1 (5 µM) and MTDR (200 nM); Formula I-1 channel: λ ex = 488nm, λ em = 490–630 nm; MTDR channel: λ ex = 639 nm, λ em = 640–700 nm; (c) Quantitative analysis of THP-1 cells co-incubated with Formula I-1 by flow cytometry after pretreatment with an endocytosis inhibitor or cooling to 4°C; (d) Time-lapse CLSM image of THP-1 cells co-incubated with Formula I-1 (5 µM); λ ex = 488 nm, λ em = 490–650 nm; (e) TEM images of mitochondrial morphology in THP-1 cells treated with 5 µM Formula I-1 for 0, 2, and 4 hours; (f) DCFH-DA (10 µM) staining in THP-1 cells treated with 5 µM Formula I-1. Green channel: λ ex = 488 nm, λ em = 490–530 nm; Red channel: λ ex = 543 nm, λ em = 600–650 nm; (g) Flow cytometry histogram of mitochondria in THP-1 cells stained with DilC1(5) after treatment with 5 µM Formula I-1; CCCP was used as a positive control for mitochondrial membrane potential depolarization; (h) Relative ATP levels in THP-1 cells after treatment with Formula I-1 (0, 1, 5 µM); cisplatin (50 µM) was used as a positive control; Data are expressed as mean ± standard deviation (n = 3); (i, j) Kinetic curves of oxygen consumption rate (OCR) after treatment with the specified concentration of Formula I-1 for 24 hours; Data are expressed as mean ± standard deviation, ****p < 0.0001, ns:p > 0.05, no statistical significance;

[0072] Figure 15 shows the proteomics target simulation and molecular docking simulation with SDHAF1 protein using Formula I, as well as the binding ability verification; (a) the target experiment workflow of Formula I-4; (b) the Nano-LC-MS / MS mass spectrum of the SDHAF1-specific peptide NPHDSTGAPETRPDGR obtained by pulling down from the THP-1 cell lysate after treatment with Formula I-4; (c) the docking conformation of Formula I-1 in the SDHAF1 cavity; (d) the MST binding curve of GFP–SDHAF1 with Formula I-1; (e) the activity of complex II in THP-1 cells treated with Formula I-1 (mean ± standard deviation, n = 3).

[0073] Figure 16 shows the mitochondrial targeting and THP-1 cytotoxicity assays of compound I-4; (a) CLSM image of THP-1 cells co-incubated with formula I-4 (5 µM) and MTDR (200 nM); Formula I-4 channel: λ ex = 488 nm, λ em = 490–630nm; MTDR channel: λ ex = 639 nm, λ em = 640–700 nm; (b) Cell viability of THP-1 cells after treatment with compound I-4 for 24 hours;

[0074] Figure 17 shows the transcriptomic analysis and apoptosis validation of compound I-1; (a) Volcano plot of differentially expressed genes (4499 in total; p-value < 0.05 after correction); (b) GO enrichment analysis of the downregulated mitochondrial energy metabolism gene set; (c) Western blot results of PARP, cleaved PARP and Bcl-2; data are expressed as mean ± standard deviation, *p < 0.001, **p < 0.0001;

[0075] Figure 18 shows a schematic diagram of I-Phe nanoparticles encapsulated with Formula I-1 and their material characterization; (a) the synthesis route of Formula I-Phe nanoparticles; (b) the zeta potentials (mean ± standard deviation, n=3) of Formula I-1, Formula I-1-NHS and Formula I-1-Phe nanoparticles; (c) the hydrodynamic diameter of Formula I-1-Phe nanoparticles as measured by dynamic light scattering; Inset: TEM image;

[0076] Figure 19 shows the in vivo treatment of acute myeloid leukemia (AML) with I-Phe nanoparticles; (a) treatment timeline of AML-carrying mice; (b, c) frequencies of leukemia cells in bone marrow (b) and peripheral blood (c) at specified time points after treatment (n=5); (d) complete blood cell counts of healthy C57BL / 6 mice (control group) and AML mice 23 days post-transplantation and those receiving specified treatment (n=5); (e) representative peripheral blood smears (Wright-Glemsa staining); (f) ex vivo images of femur, liver, and spleen 23 days post-transplantation; (g, h) weights of liver (g) and spleen (h) at the endpoint (n=5); data are expressed as mean ± standard deviation, ns: p > 0.05, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001;

[0077] Figure 20 shows H&E stained sections of major organs after intravenous injection of different concentrations of I-Phe nanoparticles for histopathological examination (scale bar = 200 μm).

[0078] Figure 21 shows the activity of cationic pyrrole derivatives in eradicating mature Candida albicans biofilms;

[0079] Figure 22 shows the fungal mitochondrial targeting ability of cationic pyrrole derivatives and their effects on mitochondrial function; (a) SEM images of the surface morphology of *Candida albicans* ATCC10231 cells treated with Formula IV-1 at a concentration of 10 × MIC for 0, 4, 6, and 8 hours; (b) CLSM images of *Candida albicans* ATCC10231 cells co-incubated with Formula IV-1 (5 × MIC) and MTDR (200 nM); Formula IV-1 channel: λ ex = 488 nm, λ em = 490–630 nm. MTDR channel: λ ex = 639 nm, λ em =640–700 nm; (c) CLSM images of mitochondria of Candida albicans ATCC10231 cells stained with DilC1(5) after treatment with Formula IV-1 (5 × MIC) for 4 h; CCCP as a positive control for mitochondrial membrane potential depolarization; Green channel: λ ex = 488nm, λ em = 490–600 nm, red channel: λ ex = 639 nm, λ em= 640–700 nm; (d) Relative ATP levels in Candida albicans ATCC10231 cells after treatment with compound IV-1 (10× MIC) for different times; data are mean ± standard deviation (n = 3), ****p < 0.0001. Detailed Implementation

[0080] The present invention will be further described in detail below with reference to embodiments, but the implementation of the present invention is not limited thereto.

[0081] Example 1 Synthesis of Compound Formula I-1:

[0082]

[0083] Compound II-1 was prepared using a pre-existing method: 1,4-diphenylbutane-1,4-dione and propargylamine (molar ratio 1:1.2) were added to a reaction flask containing toluene, with trifluoroacetic acid as a catalyst. The reaction mixture was refluxed for approximately 6 hours, followed by solvent removal under reduced pressure. The crude product was washed with a saturated aqueous sodium bicarbonate solution, extracted with dichloromethane / water, and the organic phase was collected and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography.

[0084] Formula I-1: Compound Formula II-1 (100 mg, 0.39 mmol) was dissolved in acetonitrile (20 mL), followed by the addition of Cu(ClO4)2·6H2O (145 mg, 0.39 mmol). The reaction mixture was stirred at room temperature for 30 minutes and then concentrated under reduced pressure. The reaction solution was extracted with DCM / H2O, the organic phase was collected and concentrated under reduced pressure, and further purified by silica gel column chromatography using DCM / MeOH = 95 / 5 (v / v) as the eluent. After purification, the product was obtained by recrystallization from diethyl ether, finally yielding the reddish-brown compound Formula I-1 (25 mg, yield 22.0%). The structure was characterized as follows: 1 H NMR (400 MHz, CD2Cl2)δ 7.77–7.55 (m, 13H), 7.51–7.44 (m, 10H), 7.37–7.11 (m, 7H), 6.67 (s, 1H),6.57 (s, 1H), 5.36 (s, 1H), 4.69–4.64 (m, 1H), 4.42–4.37 (m, 1H), 4.35–4.26(m, 4H), 2.51 (t, J = 2.5 Hz, 1H), 2.32 (q, J = 2.5 Hz, 2H). 13C NMR (100 MHz, CD2Cl2) δ 176.3, 174.3, 142.1, 137.0, 135.5, 135.1, 133.9, 133.8, 132.3,131.8, 131.8, 131.2, 131.0, 130.7, 130.6, 130.4, 130.2, 130.1, 130.0, 129.7,129.7, 129.5, 129.2, 129.2, 129.2, 128.6, 128.5, 128.5, 128.4, 126.5, 115.5,114.4, 112.1, 111.4, 110.9, 88.4, 80.1, 79.1, 76.0, 75.4, 74.2, 73.2, 37.3,35.9, 35.6. HRMS (ESI) m / z: [M] + calcd for C 57 H 42 N3 + : 768.3373, found:768.3372. The structural characterization is shown in Figures 1 and 5, and was clearly verified by single-crystal X-ray diffraction (Figure 9).

[0085] Example 2 Synthesis of Compound Formula I-2:

[0086]

[0087] The preparation method in this embodiment is similar to that in Example 1.

[0088] The yield of compound I-2 was 20.0%. Its structural characterization is as follows: 1 H NMR (400 MHz, CD2Cl2) δ 7.71–7.54 (m, 6H), 7.49–7.37 (m, 17H), 7.26–7.00 (m, 7H), 6.56 (s, 1H), 6.48 (s,1H), 5.22 (s, 1H), 3.93–3.61 (m, 6H), 1.20–1.12 (m, 4H), 1.02 (q, J = 7.1 Hz, 2H), 0.87–0.79 (m, 6H), 0.62 (t, J = 7.2 Hz, 3H), 0.53–0.47 (m, 6H). 13C NMR(100 MHz, CDCl3) δ 174.9, 173.2, 140.9, 135.9, 134.8, 134.5, 133.7, 133.4,132.8, 131.5, 131.4, 131.3, 130.2, 130.1, 130.02, 129.95, 129.8, 129.60,129.56, 129.45, 129.4, 129.2, 128.9, 128.8, 128.6, 128.3, 128.0, 127.9,127.3, 114.7, 114.5, 111.2, 111.1, 110.7, 88.5, 46.9, 45.0, 44.8, 32.8, 32.6,31.1, 20.1, 19.4, 13.3, 13.2. HRMS (ESI) m / z: [M] + calcd for C 60 H 60 N3 + :822.4782, found 822.4798. The structural characterization is shown in Figures 2 and 6, and was clearly verified by single-crystal X-ray diffraction (Figure 10).

[0089] Example 3: Synthesis of Compound I-3:

[0090]

[0091] The preparation method in this embodiment is similar to that in Example 1.

[0092] The yield of compound I-3 was 15.0%. Its structure was characterized as follows: 1 H NMR (400 MHz, CD2Cl2) δ 7.67–7.62(m, 2H), 7.53–7.28 (m, 20H), 7.19–7.09 (m, 6H), 7.06–6.89 (m, 10H), 6.73 (d,J = 11.6 Hz, 2H), 6.61–6.52 (m, 5H), 6.34 (d, J = 7.5 Hz, 2H), 5.48 (s, 1H), 5.29–5.09 (m, 2H), 5.06–4.94 (m, 2H), 4.93–4.77 (m, 2H). 13C NMR (150 MHz, CDCl3) δ 176.1, 173.0, 141.5, 138.4, 137.2, 136.9, 135.7, 134.2, 133.9,133.7, 133.4, 132.3, 131.55, 131.45, 131.0, 130.9, 130.8, 130.4, 130.3,130.2, 130.0, 129.9, 129.8, 129.5, 129.4, 129.30, 129.30, 129.2, 129.0,128.9, 128.8, 128.69, 128.65, 128.60, 128.56, 128.4, 128.33, 128.26, 128.2,127.8, 127.7, 127.64, 127.61, 127.2, 126.8, 126.6, 126.0, 125.9, 125.5,115.6, 115.3, 111.8, 111.6, 111.1, 89.2, 50.7, 48.8, 48.6. HRMS (ESI) m / z:[M] + calcd for C 69 H 54 N3 + : 924.4312, found 924.4304.

[0093] Example 4 Synthesis of Compound Formula I-4:

[0094]

[0095] The preparation method of Formula II-4 is the same as that in Example 1 of this document.

[0096] Compound II-5: Compound II-4 (291 mg, 1.0 mmol) was dissolved in dichloromethane (10 mL), followed by the addition of p-toluenesulfonyl chloride (191 mg, 1.0 mmol) and triethylamine (695 μL). The reaction mixture was stirred at room temperature for 4 hours, and then concentrated under reduced pressure. The mixture was extracted with DCM / H2O, the organic phase was collected and concentrated under reduced pressure, and further purified by silica gel column chromatography using PE / EA = 83 / 17 (v / v) as eluent to give compound II-5 (311 mg, 70% yield). The structure was characterized as follows: 1H NMR (400 MHz, CD2Cl2) δ 7.61–7.48(m, 3H), 7.43–7.41 (m, 7H), 7.36–7.30 (m, 4H), 6.22 (s, 2H), 4.08 (t, J = 6.6Hz, 2H), 3.54 (t, J = 6.3 Hz, 2H), 2.45 (s, 3H), 1.17–1.10 (m, 2H), 1.08–1.03 (m, 2H). 13 C NMR (150 MHz, CD2Cl2) δ 145.3, 137.2, 134.3, 133.3, 130.2, 129.1,129.0, 128.1, 127.4, 110.1, 70.2, 44.7, 26.7, 25.6, 21.8. HRMS (ESI) m / z: [M+H] + calcd for C 27 H 28 NO3S + : 446.1790, found 446.1780.

[0097] Compound II-6: Compound II-5 (178 mg, 0.4 mmol) was dissolved in N,N-dimethylformamide (15 mL), followed by the addition of biotin (98 mg, 0.4 mmol) and potassium carbonate (83 mg, 0.6 mmol). The reaction mixture was heated to 60 °C and reacted for 12 hours. The mixture was then extracted with DCM / H₂O, the organic phase was collected and concentrated under reduced pressure, and further purified by silica gel column chromatography using EA / MeOH = 80 / 20 (v / v) as eluent to give compound II-6 (148 mg, 71% yield). The structure was characterized as follows: 1H NMR (400 MHz, CD2Cl2) δ 7.47–7.41 (m, 8H), 7.36–7.31 (m, 2H), 6.24 (s, 2H), 5.17 (s, 1H), 4.94 (s, 1H),4.50–4.45 (m, 1H), 4.29–4.24 (m, 1H), 4.13 (t, J = 7.0 Hz, 2H), 3.64 (t, J =6.4 Hz, 2H), 3.16–3.11 (m, 1H), 2.93–2.88 (m, 1H), 2.69 (d, J = 12.8 Hz, 1H),2.15 (t, J = 7.4 Hz, 2H), 1.62 (d, J = 8.4 Hz, 4H), 1.41–1.32 (m, 2H), 1.25–1.19 (m, 2H), 1.11–1.07 (m, 2H). 13 C NMR (150 MHz, CD2Cl2) δ 173.7, 164.2,137.0, 134.4, 129.1, 128.9, 127.3, 110.0, 63.7, 62.3, 60.5, 55.9, 45.1, 41.0,34.1, 28.7, 28.6, 27.4, 25.5, 25.1. HRMS (ESI) m / z: [M+Na] + calcd forC 30 H 35 N3NaO3S + : 540.2297, found 540.2291.

[0098] Compound I-4: Compound II-6 (103 mg, 0.2 mmol) was dissolved in acetonitrile (20 mL), followed by the addition of Cu(ClO4)2·6H2O (74 mg, 0.2 mmol). The reaction mixture was stirred at room temperature for 30 minutes and then concentrated under reduced pressure. The mixture was extracted with DCM / H2O, the organic phase was collected and concentrated under reduced pressure, and further purified by silica gel column chromatography using DCM / MeOH = 85 / 15 (v / v) as eluent to give a reddish-brown solid, compound I-4 (10 mg, 9% yield). The structure was characterized as follows: ¹H NMR (400 MHz, CD₂Cl₂) δ 7.64–7.58 (m, 7H), 7.50–7.46 (m, 15H), 7.39–7.36 (m, 2H), 7.29–7.25 (m, 3H), 7.07 (d, J = 7.2 Hz, 3H), 6.58 (s, 1H), 6.47 (s, 1H), 6.08 (d, J = 48.6 Hz, 2H), 5.82 (d, J = 8.9 Hz, 2H), 5.75–5.68 (m, 2H), 5.25 (d, J = 2.4 Hz, 1H), 4.52–4.48 (m, 3H), 4.31–4.26 (m, 3H), 3.76–3.71 (m, 6H), 3.70–3.60 (m, 6H), 3.16–3.10 (m, 3H), 2.92–2.87 (m, 3H), 2.73 (d, J = 12.7 Hz, 3H), 2.19–2.10 (m, 6H), 1.73–1.49 (m,12H), 1.38–1.22 (m, 14H), 1.13 (s, 6H). HRMS (ESI) m / z: [M] + calcd forC 90 H 102 N9O9S3 + : 1548.6957, found 1548.6965.

[0099] Example 5 Synthesis of Compound IV-1:

[0100]

[0101] Compound III-1 was prepared using an existing method: Compound II-1 (257 mg, 1.0 mmol) was dissolved in dichloromethane (30 mL), followed by dropwise addition of a MeNO2 solution containing ferric chloride (324 mg, 2 mmol). The solution color changed from pale yellow to reddish-brown, and the mixture was stirred at room temperature for 3.5 hours. After the reaction was complete, the mixture was extracted with DCM / H2O. The organic phase was collected, concentrated under reduced pressure, and further purified by silica gel column chromatography using PE / DCM = 67 / 33 (v / v) as the eluent to obtain a white solid compound III-1 (150 mg, yield 58.6%).

[0102] Compound IV-1: Compound III-1 (70 mg, 0.13 mmol) and indole (15 mg, 0.13 mmol) were dissolved in acetonitrile (10 mL), followed by the addition of Cu(ClO4)2·6H2O (48 mg, 0.13 mmol). After stirring at room temperature for 1 hour, the mixture was concentrated under reduced pressure. Extraction was performed with DCM / H2O, and the organic phase was collected and concentrated under reduced pressure. Further purification was carried out by silica gel column chromatography using pure EA as the eluent to obtain a reddish-brown solid, compound IV-1 (25 mg, yield 26.5%). The structure was characterized as follows: 1 H NMR (400 MHz, CD2Cl2)10.04 (s, 1H), 7.73–7.50 (m, 16H), 7.43–7.33 (m, 5H), 7.28–7.15 (m, 3H), 7.06 (t, J = 7.4 Hz, 1H), 6.23 (s, 1H), 6.02(s, 1H), 4.55 (d, J = 18.2 Hz, 1H), 4.36 (d, J = 39.3 Hz, 3H), 2.87 (d, J =35.8 Hz, 1H), 2.58 (s, 1H), 2.47 (s, 1H), 2.07 (s, 1H). 13 C NMR (100 MHz, CD2Cl2) δ 175.2, 137.7, 135.2, 133.2, 130.9, 130.82, 130.79, 130.4, 130.2, 130.1, 130.0, 129.8, 129.6, 129.0, 128.6, 127.0, 123.3, 121.2, 119.5, 115.8,110.2, 105.3, 75.9, 37.5, 36.2. [M] + calcd for C 46 H34 N3 + : 628.2748, found628.2750. The structural characterization is shown in Figures 3 and 7.

[0103] Example 6 Synthesis of Compound IV-2:

[0104]

[0105] The preparation method in this embodiment is similar to that in Example 5. The yield of compound IV-2 was 21.0%. The structure was characterized as follows: 1 HNMR (400 MHz, CD2Cl2)7.72–7.65 (m, J = 11.8, 7.9 Hz, 11H), 7.61–7.55 (td, J =10.2, 8.7, 5.4 Hz, 10H), 7.52–7.47 (m, 2H), 7.41 (s, 4H), 7.34–7.24 (m, 3H), 7.17 (d, J = 7.2 Hz, 1H), 6.34 (s, 1H), 6.08 (s, 1H), 4.67– 4.62 (m, J =18.1, 2.5 Hz, 1H), 4.52–4.47 (m, J = 18.1, 2.5 Hz, 1H), 4.34–4.32 (m, J =5.0, 2.5 Hz, 2H), 2.87 (d, J = 36.5 Hz, 1H), 2.48 (t, J = 2.4 Hz, 1H), 2.03(t, J = 2.4 Hz, 1H). 13 C NMR (100 MHz, CD2Cl2) δ 138.8, 137.7, 137.6, 135.5,133.1, 132.6, 131.0, 130.9, 130.8, 130.6, 130.5, 130.3, 129.9, 129.6, [M] + calcd for C 52 H 38 N3 + : 704.3061, found704.3047. The structural characterization is shown in Figure 4 and Figure 8.

[0106] Example 7: Photophysical characterization of cationic pyrrole compounds:

[0107] The photophysical properties of cationic pyrrole compounds were investigated. These pyrrole compounds (Formulas I-1 to I-3 and Formulas IV-1 to IV-2) exhibited maximum absorption and emission wavelengths of ~465 nm and ~600 nm, respectively, in dimethyl sulfoxide (Figure 11). This can be attributed to their intramolecular charge transfer characteristics, where the 3′′-pyrrole group acts as an electron donor group and the 2′H-pyrrole-1′-onium moiety acts as an electron acceptor group. Simultaneously, the cationic pyrrole compounds also exhibited AIE behavior. Taking Formula I-1 as an example, fluorescence gradually increased with increasing water content in the DMSO / H2O mixture (Figure 12). This can be attributed to the restricted intramolecular motion in the aggregated state and the suppression of π-π stacking-induced fluorescence quenching by the distorted molecular structure. In the ethanol / glycerol mixture, the emission of compound I-1 gradually increased with increasing viscosity, which can be attributed to the restriction of intramolecular motion in the high-viscosity medium. Furthermore, the quantum yield and fluorescence lifetime were tested in different solutions and in polymethyl methacrylate (PMMA) films (as shown in Table 1, the concentrations of compounds I-1 to I-3 were all 50 μM).

[0108] Table 1. Maximum absorption wavelength, maximum emission wavelength, quantum yield, and fluorescence lifetime of cationic pyrrole compounds in different solutions and PMMA films.

[0109]

[0110] Example 8: Cytotoxicity, subcellular imaging, and cytotoxic mechanism of cationic pyrrole compounds:

[0111] Of the formulas I-1 to I-3, formula I-1 exhibited the highest cytotoxicity, showing the highest IC50 value against THP-1, PaTu-8988t, and MCF-7 cells. 50The values ​​were 1.99 µM, 3.43 µM, and 3.46 µM, respectively (Fig. 13 and Fig. 14A). Confocal laser scanning microscopy (CLSM) images showed that Formula I-1 selectively stained mitochondria, which was validated by the Mito-Tracker Deep Red overlap experiment, showing high Pearson correlation coefficients (0.83–0.92) in all three cancer cell lines (Fig. 14B). Cellular uptake was subsequently tracked by flow cytometry using its AIE properties. THP-1 cells pretreated with endocytosis inhibitors (sodium azide / 2-deoxy-D-glucose, chloroquine, chlorpromazine, nystatin, methyl-β-cyclodextrin, hypertonic sucrose) did not show a decrease in fluorescence intensity relative to the control group (Fig. 14C). Conversely, cooling THP-1 cells to 4°C reduced the fluorescence signal by 60%, confirming that the uptake of Formula I-1 is energy-dependent and not mediated by endocytosis.

[0112] Given the selective accumulation of ionic pyrrole compounds in mitochondria, CLSM and transmission electron microscopy (TEM) were subsequently used to examine the mitochondrial morphological changes induced by Formula I-1. CLSM imaging of THP-1 cells exposed to 5 µM of Formula I-1 showed that mitochondrial swelling was progressive and time-dependent, becoming apparent at 15 min and significant at 30, 45, and 60 min post-treatment (Fig. 14, D). TEM images acquired at 1 and 4 hours further confirmed mitochondrial swelling and vacuolation (Fig. 14, E). The mitochondrial dysfunction induced by Formula I-1 in THP-1 cells was further characterized by increased reactive oxygen species (ROS), depolarization of mitochondrial membrane potential, and decreased ATP levels (Fig. 14, F–H).

[0113] The effects of Formula I-1 on mitochondrial OXPHOS and glycolytic activity were assessed. Real-time analysis of oxygen consumption rate (OCR) showed that exposure to Formula I-1 effectively inhibited OXPHOS, specifically by a 46% reduction in basal respiration, a 75% inhibition of ATP-related respiration, a 49% decrease in maximum respiratory capacity, and a 56% decrease in reserve respiratory capacity (Figure 14, I). Meanwhile, extracellular acidification rate (ECAR), an indirect indicator of glycolytic flux, showed no significant change compared to the untreated control group (Figure 14, J). These results indicate that Formula I-1 selectively impairs mitochondrial OXPHOS without affecting glycolytic activity.

[0114] Formulas I-2 to I-3, and IV-1 to IV-2 also specifically target mitochondria.

[0115] Example 9: Identification of SDHAF1 as a direct target using chemical proteomics:

[0116] To identify the mitochondrial protein targets of the cationic pyrrole compound Formula I backbone, biotinylated probes were synthesized for chemical proteomics targeting experiments (Figure 15). Formula I-4 was validated in vitro, demonstrating its continued mitochondrial-specific targeting and highly effective killing of THP-1 (Figure 16). After treatment with Formula I-4, THP-1 cells were lysed, and the biotinylated protein was pulled down using streptavidin magnetic beads. Nano-LC-MS / MS identified the SDHAF1-specific peptide NPHDSTGAPETRPDGR, confirming the selective binding of the Formula I backbone to SDHAF1 (Figure 15a, b). Molecular docking predicted the binding free energy between Formula I-1 and SDHAF1 to be approximately -8.2 kcal / mol. -1 The benzene ring and alkynyl group of formula I-1 were positioned within the cavity of SDHAF1, in contact with Leu-12, Val-11, Phe-36, Arg-37, His-39, Ala-40, Leu-42, Arg-44, and His-4 (Figure 15c). Micro-thermophoresis (MST) measurements yielded the dissociation constant (Ki) of the interaction between formula I-1 and SDHAF1. d The concentration of SDHAF1 was 242 nM, confirming their high affinity binding (Fig. 15d). Given that SDHAF1 is an important assembler of mitochondrial complex II, the binding of formula I-1 to SDHAF1 significantly reduced complex II activity, as shown in Fig. 15e. The reduction in complex II activity is consistent with the observed impaired oxidative phosphorylation, as shown in Fig. 15e.

[0117] The molecular docking simulation binding energies of cationic pyrrole compounds are shown in Table 2.

[0118] Table 2. Simulated binding energies of cationic pyrrole compounds via molecular docking

[0119]

[0120] Example 10: Induction of apoptosis by cationic pyrrole compound formula I:

[0121] To further elucidate the cytotoxic mechanism of Formula I-1 in THP-1 cells, RNA sequencing (RNA-seq) was performed to identify differentially expressed genes associated with cell death pathways. RNA-seq of THP-1 cells exposed to Formula I-1 for 24 hours revealed 4499 differentially expressed genes (2627 upregulated; 1872 downregulated) (Figure 17a). Gene set enrichment analysis showed a significant downregulation of mitochondrial energy metabolism genes, including ATP synthesis and ATP hydrolysis activity (Figure 17b), indicating mitochondrial damage. Western blot analysis further revealed reduced full-length PARP, increased cleaved PARP, and decreased Bcl-2 levels (Figure 17c), indicating that Formula I-1 induces apoptosis in THP-1 cells.

[0122] Example 11: Study on the in vivo treatment of acute myeloid leukemia with Formula I-1-Phe NPs:

[0123] To improve the water solubility and system circulation capacity of formula I-1, it was encapsulated in the amphiphilic polymer DSPE-PEG using a nanoprecipitation method. 2000 In -COOH, nanoparticles of formula I-1 were obtained (Figure 18a). To further enhance the uptake by leukemia cells, L-phenylalanine was modified on the surface of the nanoparticles of formula I-1 to obtain nanoparticles of formula I-1-Phe (Figure 18a, b). Dynamic light scattering analysis showed that the nanoparticles of formula I-1-Phe were well dispersed in aqueous solution, and the hydrodynamic diameter (D) was [missing information]. H The zeta potential (ζ) is 103±2 nm and -22±2 mV (Fig. 18c). TEM images further confirm the monodispersity and uniformity of the I-1-Phe nanoparticles (Fig. 18c inset).

[0124] To evaluate the in vivo anti-AML effects of cationic pyrrole compounds (e.g., Formula I-1), an syngeneic mouse model was used. This model was established by irradiating mice with a sublethal dose followed by transplantation of bone marrow cells transduced with the MLL-AF9 fusion gene (MSCV-MLL-AF9-IRES-GFP). On day 18, leukemia mice were randomly assigned (n=5 per group) to receive either saline or Formula I-1-Phe nanoparticles at doses of 0.25, 0.50, or 1.00 mg / kg via tail vein injection, with a second injection on day 20. Endpoint analysis was performed on day 23. AML mice treated with Formula I-1-Phe nanoparticles showed a dose-dependent reduction in leukemia burden in both bone marrow and peripheral blood (Figure 19, ac). Complete blood counts showed a dose-dependent return to normal white blood cell counts, and restoration of neutrophil, erythrocyte, and platelet levels (Figure 19, d). Peripheral blood smears showed a dose-dependent reduction in leukemia blasts, while spleen and liver weight and histological structure returned to healthy ranges (eh in Figure 19). Hematoxylin and eosin (H&E) staining of major organs showed no significant toxicity or inflammatory lesions compared to the control group, indicating the biosafety of formula I-1-Phe nanoparticles (Figure 20).

[0125] Example 12 In vitro antibacterial activity of cationic pyrrole compounds I-1 to I-3 and IV-1 to IV-2:

[0126] (1) The antibacterial activities of compounds I-1 to I-3 and IV-1 to IV-2 were studied. For Candida albicans ATCC10231 (Guangdong Provincial Microbial Culture Collection Center), the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of compound IV-1, which incorporates an indole group, were 3.13 μM and 6.25 μM, respectively (Table 3). Meanwhile, compounds I-1 and IV-2 also exhibited low MIC values ​​of 6.25 μM and MFC values ​​(12.5–25 μM) (Table 3). Notably, compounds I-3, IV-1, and IV-2 exhibited low hemolytic activity, with low HC... 10 The concentration (causing 10% hemolysis) is greater than 100 μM. According to HC... 10 The selectivity index (SI) calculated by / MIC is greater than 32 (Table 3), which indicates that Formula IV-1 has good biocompatibility and is expected to be a preferred molecule for anti-Candida albicans.

[0127] Table 3. Antifungal and hemolytic activities of cationic pyrrole compounds of formulas I-1 to I-3 and IV-1 to IV-2.

[0128]

[0129] (2) Studies have shown that fungal biofilms can significantly reduce the sensitivity of fungi to antimicrobial agents and enhance the spread of drug resistance. Taking IV-1 as an example, the activity of cationic pyrrole compounds in eradicating mature Candida albicans biofilms was further studied, and the results are shown in Figure 21. At the same concentration, formula IV-1 has a better ability to eradicate fungal biofilms, comparable to that of amphotericin B. In contrast, the antibiotic control group, fluconazole, could not effectively eradicate mature fungal biofilms. Even at a high concentration of 200 μM, 92.1% of fungal cells still survived within the biofilm.

[0130] (3) Study the fungal mitochondrial targeting ability and its effect on mitochondrial function. Taking compound IV-1 as an example, the dynamic effect of drug treatment on the morphology of Candida albicans cells was first observed by scanning electron microscopy (SEM). As shown in Figure 22a, the untreated Candida albicans cells had a smooth surface and intact structure; however, after treatment with IV-1 (10 × MIC) for different times, the cell morphology changed significantly: after 4 h of treatment, the cell surface showed slight wrinkling; after 6 h, the wrinkling was obvious; and by 8 h, the cell morphology was severely deformed and obvious cracks appeared.

[0131] Furthermore, utilizing the compound's inherent AIE properties, its subcellular localization within fungal cells was investigated. Candida albicans was treated with IV-1 (5×MIC) for 4 h, then co-incubated with the commercial mitochondrial dye Mito-Tracker Deep Red (MTDR). Immediately after washing, confocal laser scanning microscopy (CLSM) was used for observation. The results, shown in Figure 22b, indicate that both green fluorescence (pseudocolor) from IV-1 and red fluorescence signals from MTDR were simultaneously observed in the drug-treated cells. Software analysis revealed a high degree of co-localization, with a Pearson correlation coefficient of 0.89, suggesting that this cationic pyrrole derivative can specifically target fungal mitochondria.

[0132] Based on the aforementioned targeting properties, the effect of Formula IV-1 on fungal mitochondrial function was further investigated. The mitochondrial membrane potential-sensitive dye DilC1(5) was used for detection: the dye emitted bright red fluorescence when the normal mitochondrial membrane potential was high, and the red fluorescence weakened or even disappeared when the membrane potential decreased. As shown in Figure 22c, the untreated group cells exhibited significant red fluorescence; however, after treatment with the mitochondrial uncoupling agent CCCP (20 μM, positive control), the red fluorescence was significantly weakened, indicating a loss of membrane potential. In the IV-1 treatment group, only the green fluorescence of the compound itself was visible, while the red fluorescence of DilC1(5) was almost completely absent, indicating that this compound also caused a decrease in fungal mitochondrial membrane potential. In summary, cationic pyrrole compounds can target fungal mitochondria, disrupt their membrane potential, and impair mitochondrial function, thereby interfering with fungal energy metabolism. To verify this effect, the changes in intracellular ATP levels in fungal cells after treatment with Formula IV-1 (10 × MIC) were detected. As shown in Figure 22d, with prolonged treatment time, the intracellular ATP content gradually decreased, reaching approximately 90% lower than the control group by 4 h. This result further confirms that the compound can significantly inhibit the energy metabolism process of fungal cells by affecting mitochondrial function.

[0133] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A cationic pyrrole compound with aggregation-induced emission properties, characterized in that: Its structure is Equation I or Equation IV. Formula IV: In Equation I, R 1 R 2 R 5 For independent hydrogen, halogen, alkyl, alkylene-R', alkyloxy, alkylcarbonyl, alkylthio, aryl, cyano, nitro, The aryl group is phenyl, hydroxylated phenyl, methoxylated phenyl, amino-substituted phenyl, or ester-substituted phenyl; in the alkylene-R' group, R' is alkynyl or aryl; R 3 R 4 For hydrogen; in formula IV, R 1 R 2 R 5 For independent hydrogen, halogen, alkyl, alkylene-R', alkyloxy, alkylcarbonyl, alkylthio, aryl, cyano, nitro, The aryl group is phenyl, hydroxylated phenyl, methoxylated phenyl, amino-substituted phenyl, or ester-substituted phenyl; in the alkylene-R' group, R' is alkynyl or aryl; R 4 R is hydrogen; R is indole, N-methylindole, N-phenylindole, naphthyl, or anthracene; Y in formula I or formula IV is ClO4. - SbF6 - Cl - .

2. The cationic pyrrole compound with aggregation-induced emission properties according to claim 1, characterized in that: In formula I, the R 2 R 5 Each is a phenyl group; R 3 R 4 It is hydrogen; the R 1 Alkyl, ethynylmethylene, ethynylethyl, benzyl In formula IV, the R 2 R 5 Each is a phenyl group; R 4 It is hydrogen; the R 1 Alkyl, ethynylmethylene, ethynylethyl, benzyl R represents indole, N-methylindole, or N-phenylindole.

3. The method for preparing the cationic pyrrole compound with aggregation-induced emission properties according to any one of claims 1 to 2, characterized in that: Includes the following steps: The compound of formula II was oxidized to obtain a cationic pyrrole compound with the structural formula of formula I; Alternatively, the compound of formula III, the oxidant, and the nucleophile can be mixed and reacted to obtain a cationic pyrrole compound with the structural formula of formula IV; Compound II is of Formula III and compound III is of Formula II: Formula III: In formula II, R 1 R 2 R 5 For independent hydrogen, halogen, alkyl, alkylene-R', alkyloxy, alkylcarbonyl, alkylthio, aryl, cyano, nitro, The aryl group is phenyl, hydroxylated phenyl, methoxylated phenyl, amino-substituted phenyl, or ester-substituted phenyl; in alkylene-R', R' is alkynyl or aryl; in Formula II, R 3 R 4 For hydrogen; R in formula III 1 R 2 R 5 For independent hydrogen, halogen, alkyl, alkylene-R', alkyloxy, alkylcarbonyl, alkylthio, aryl, cyano, nitro, The aryl group is phenyl, hydroxylated phenyl, methoxylated phenyl, amino-substituted phenyl, or ester-substituted phenyl; in alkylene-R', R' is alkynyl or aryl; in Formula III, R 4 The nucleophile is hydrogen; the nucleophile is one of indole, N-methylindole, N-phenylindole, naphthalene, and anthracene; in the oxidation of the compound of formula II, the oxidation refers to oxidation with an oxidizing agent; the oxidizing agent is copper perchlorate, ferric chloride, or silver hexafluoroantimonate; in the mixed reaction, the oxidizing agent is copper perchlorate or silver hexafluoroantimonate.

4. The method for preparing the cationic pyrrole compound with aggregation-induced emission properties according to claim 3, characterized in that: In alkylene-R', the alkylene group is methylene or ethylene; in R', the aryl group is phenyl, and the ynyl group is ethynyl or propynyl; R in formulas II and III 2 R 5 Each is a phenyl group; R in Formula II 1 Alkyl, ethynylmethylene, ethynylethyl, benzyl R in Formula III 1 Alkyl, ethynylmethylene, ethynylethyl, benzyl The oxidation is carried out in a solvent; when the oxidant is copper perchlorate, silver hexafluoroantimonate, or ferric chloride, the oxidation is carried out using an organic solvent as the reaction medium; the organic solvent is one or more of acetonitrile, dichloromethane, and methanol; in mixed reactions, an organic solvent is used as the reaction medium; the organic solvent is one or more of acetonitrile, dichloromethane, and methanol; the compound of formula III is prepared by the following method: using ferric chloride as the oxidant, the compound of formula II is oxidized to obtain the compound of formula III; in the preparation of the cationic pyrrole compound, the oxidation temperature is 20~30 °C; the oxidation time is 0.2~8 hours; the molar ratio of the compound of formula II to the oxidant is 1:(0.9~1.2); the molar ratio of the compound of formula III to the nucleophilic compound and the oxidant is 1:(0.9~1.2). (0.9~1.2); After the oxidation reaction of compound II is complete, it is concentrated under reduced pressure, extracted, and purified by column chromatography with dichloromethane / methanol as the eluent; After the reaction of compound III with nucleophilic reagent is complete, it is concentrated under reduced pressure, extracted, and purified by column chromatography with ethyl acetate as the eluent.

5. The application of the cationic pyrrole compound with aggregation-induced emission properties according to any one of claims 1 to 2, characterized in that: The cationic pyrrole compound with aggregation-induced emission properties is used to prepare SDHAF1 inhibitors, mitochondrial-specific fluorescent imaging agents, formulations that inhibit the activity of mitochondrial complex II, and / or antifungal agents; the cationic pyrrole compound with aggregation-induced emission properties has the structure of Formula I and / or Formula IV. Formula IV: In formula I, R 1 R 2 R 5 For independent hydrogen, halogen, alkyl, alkylene-R', alkyloxy, alkylcarbonyl, alkylthio, aryl, cyano, nitro, The aryl group is phenyl, hydroxylated phenyl, methoxylated phenyl, amino-substituted phenyl, or ester-substituted phenyl; in alkylene-R', R' is alkynyl or aryl; in Formula I, R 3 R 4 For hydrogen; R in formula IV 1 R 2 R 5 For independent hydrogen, halogen, alkyl, alkylene-R', alkyloxy, alkylcarbonyl, alkylthio, aryl, cyano, nitro, The aryl group is phenyl, hydroxylated phenyl, methoxylated phenyl, amino-substituted phenyl, or ester-substituted phenyl; in alkylene-R', R' is alkynyl or aryl; in formula IV, R 4 R is hydrogen; R is indole, N-methylindole, N-phenylindole, anthracene, or naphthyl; Y in formula I or formula IV is ClO4. - SbF6 - Cl - .

6. A mitochondrial succinate dehydrogenase assembly factor 1 inhibitor, characterized in that: This includes cationic pyrrole compounds with aggregation-induced emission properties; the cationic pyrrole compounds with aggregation-induced emission properties are of formula I and / or formula IV. Formula IV: In formula I, R 1 R 2 R 5 For independent hydrogen, halogen, alkyl, alkylene-R', alkyloxy, alkylcarbonyl, alkylthio, aryl, cyano, nitro, The aryl group is phenyl, hydroxylated phenyl, methoxylated phenyl, amino-substituted phenyl, or ester-substituted phenyl; in alkylene-R', R' is alkynyl or aryl; in Formula I, R 3 R 4 For hydrogen; R in formula IV 1 R 2 R 5 For independent hydrogen, halogen, alkyl, alkylene-R', alkyloxy, alkylcarbonyl, alkylthio, aryl, cyano, nitro, The aryl group is phenyl, hydroxylated phenyl, methoxylated phenyl, amino-substituted phenyl, or ester-substituted phenyl; in alkylene-R', R' is alkynyl or aryl; in formula IV, R 4 R is hydrogen; R is indole, N-methylindole, N-phenylindole, anthracene, or naphthyl; Y in formula I or formula IV is ClO4. - SbF6 - Cl - .

7. The mitochondrial succinate dehydrogenase assembly factor 1 inhibitor according to claim 6, characterized in that: In formula I, the R 2 R 5 Each is a phenyl group; R 3 R 4 It is hydrogen; the R 1 Alkyl, ethynylmethylene, ethynylethyl, benzyl In equation IV, R 2 R 5 It is phenyl; R 4 It is hydrogen; the R 1 Alkyl, ethynylmethylene, ethynylethyl, benzyl R represents indole, N-methylindole, or N-phenylindole.

8. The application of the mitochondrial succinate dehydrogenase assembly factor 1 inhibitor according to claim 6 or 7, characterized in that: The mitochondrial succinate dehydrogenase assembly factor 1 inhibitor is used to prepare antitumor drugs; the antitumor drugs include drugs for the prevention and / or treatment of acute myeloid leukemia, antipancreatic cancer drugs, and / or anti-breast cancer drugs.

9. The application according to claim 8, characterized in that: The antitumor drug is prepared as a complex by combining a mitochondrial succinate dehydrogenase assembly factor 1 inhibitor as defined in claim 6 or 7 with a functionalized carrier through a nano-assembly process; the functionalized carrier includes the amphiphilic polymer DSPE-PEG-COOH, and the complex is in the form of nanoparticles; the surface of the complex is modified with L-phenylalanine; the mitochondrial succinate dehydrogenase assembly factor 1 inhibitor is a cationic pyrrole compound with aggregation-induced emission properties, specifically as defined in claim 6 or 7.

10. A fluorescent imaging agent for mitochondrial-specific fluorescence imaging, characterized in that: This includes cationic pyrrole compounds with aggregation-induced emission properties; the cationic pyrrole compounds with aggregation-induced emission properties are of formula I and / or formula IV. Formula IV: In formula I, R 1 R 2 R 5 For independent hydrogen, halogen, alkyl, alkylene-R', alkyloxy, alkylcarbonyl, alkylthio, aryl, cyano, nitro, The aryl group is phenyl, hydroxylated phenyl, methoxylated phenyl, amino-substituted phenyl, or ester-substituted phenyl; in alkylene-R', R' is alkynyl or aryl; in Formula I, R 3 R 4 For hydrogen; R in formula IV 1 R 2 R 5 For independent hydrogen, halogen, alkyl, alkylene-R', alkyloxy, alkylcarbonyl, alkylthio, aryl, cyano, nitro, The aryl group is phenyl, hydroxylated phenyl, methoxylated phenyl, amino-substituted phenyl, or ester-substituted phenyl; in alkylene-R', R' is alkynyl or aryl; in formula IV, R 4 R is hydrogen; R is indole, N-methylindole, N-phenylindole, anthracene, or naphthyl; Y in formula I or formula IV is ClO4. - SbF6 - Cl - .

Images