Use of compound HEX and / or compound POM-HEX in medicine for the prevention and / or treatment of fungal infections

Abstract

The application provides an application of a compound HEX and / or a compound POM-HEX in medicine for preventing and / or treating fungal infection, and belongs to the technical field of medicine. In vitro experiments show that POM-HEX alone has inhibiting effects on candida and cryptococcus, and when combined with fluconazole, the antifungal activity can be significantly improved, and the drug-resistant strains can restore the sensitivity to fluconazole. The organ bacterial load experiment in mice in vivo proves that POM-HEX can stably exert the drug efficacy in the organism. In addition, the IC 50 value of the metabolic product HEX of POM-HEX for inhibiting the Eno1 enzyme activity of Candida albicans is 1 / 30 of the IC 50 of HEX for inhibiting the Eno1 enzyme activity of human. The application discloses that the HEX and / or the compound have strong antifungal activity and high selectivity for the target point Eno1, provides a new idea for antifungal treatment, the drug combination can reduce the drug dosage, reduce the toxic and side effects, and solves the problem of fungal drug resistance.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medicine, and particularly relates to application of a compound HEX and / or a compound POM-HEX in a medicine for preventing and / or treating fungal infection. BACKGROUND

[0002] Invasive fungal disease (IFDs) affects more than a billion people and is an important cause of death in critically ill patients. With the increase in the use of organ transplantation, broad-spectrum antibacterial drugs and immunosuppressive agents, the number of immunocompromised people continues to increase in IFDs-related medical investment. Antifungal drugs are mainly divided into azoles, polyenes and echinocandins. The existing antifungal treatment has a long cycle, large side effects, and is prone to drug resistance, which leads to treatment failure, and new antifungal drugs or synergists with high efficiency and low toxicity are urgently needed.

[0003] Enolase catalyzes the conversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP), and is widely distributed in the tissues and cells of various organisms as a key enzyme of glycolysis. Enolase is mainly located inside the Candida albicans cell, and can also be released into the blood during IFDs, so the detection of serum anti-enolase antibodies and antibody titers serves as an auxiliary diagnosis of deep candidiasis. However, there is no research on antifungal drugs targeting enolase.

[0004] HEX is an artificially synthesized phosphonate compound, and its structure is similar to that of 2-PG, which is a substrate competitive enolase inhibitor. POM-HEX is a prodrug of HEX, and has stronger cell permeability and can specifically inhibit ENO2 of glioma cells. HEX / POM-HEX has antitumor and antibacterial parasitic activities, and is disclosed in patent PCT / US2016 / 021609. The structural formula of HEX / POM-HEX is as follows:

[0005] .

[0006] However, there is no research on the antifungal effect of HEX / POM-HEX in the prior art, and there is no report on the inhibitory activity of HEX / POM-HEX on enolase of different species. SUMMARY

[0007] The present application is carried out to solve the above problems, and aims to provide application of a compound HEX and / or a compound POM-HEX in a medicine for preventing and / or treating fungal infection.

[0008] The present application provides application of a compound HEX and / or a compound POM-HEX in a medicine for preventing and / or treating fungal infection, wherein the structural formula of the compound HEX is as follows:

[0009] ,

[0010] The structural formula of the compound POM-HEX is as follows:

[0011] .

[0012] In the application provided by the present application, the fungus can further include Candida, mold and Cryptococcus.

[0013] In the application provided by the present application, the fungus can further include standard strains and clinical strains.

[0014] In the application provided by the present application, the fungus can further include strains resistant or sensitive to fluconazole.

[0015] In the application provided by the present application, the fungus can further include sensitive strains: sensitive Candida albicans (SC5314, 395, 538, 1171), Candida krusei ATCC4969, Candida parapsilosis ATCC90081, Candida tropicalis ATCC8915, Candida glabrata 537, Cryptococcus neoformans (H99, 443, 444, 445), Cryptococcus gattii (D2, D2r); and resistant strains: resistant Candida albicans 103, Aspergillus fumigatus 7544.

[0016] In the application provided by the present application, the application can further include that the compound HEX and / or the compound POM-HEX is used in combination with at least one of fluconazole, voriconazole, itraconazole, posaconazole, amphotericin B and its liposome, caspofungin and anidulafungin.

[0017] In the application provided by the present application, the drug for preventing and / or treating fungal infection can further include the compound HEX and / or the compound POM-HEX and pharmaceutically acceptable salts thereof.

[0018] In the application provided by the present application, the drug for preventing and / or treating fungal infection can further include the compound HEX and / or the compound POM-HEX and a pharmaceutically acceptable carrier or excipient.

[0019] In the application provided by the present application, the pharmaceutically acceptable carrier or excipient can further include one or more of the following: an auxiliary, a wetting agent, an emulsifying agent, a suspending agent, a preservative, a salt affecting osmotic pressure, a buffer, a sweetener, a flavoring agent or a coloring agent.

[0020] In the application provided by the present application, the application can also have the following features: wherein the application comprises the use of compound HEX and / or compound POM-HEX to prevent and / or treat fungal infection by improving the selectivity of enolase target, reducing MIC value, inhibiting fungal growth, inhibiting hyphae formation, inhibiting bud formation of fungal body, and reducing the load of organs in vivo.

[0021] Effects of the application

[0022] In vitro cell experiments show that POM-HEX alone can inhibit Candida albicans and Cryptococcus neoformans, and the minimum inhibitory concentration MIC thereof is 4-32 μg / mL. POM-HEX can reduce the load of Cryptococcus neoformans H99 infected mouse brain tissue and lung tissue (p<0.0001). When POM-HEX is used in combination with antifungal drug fluconazole, the inhibitory concentration of fluconazole can be significantly reduced, especially for fluconazole-resistant strains (Candida albicans 103 and Aspergillus fumigatus 7544), which has an inhibitory effect on the drug-resistant fungi, so that the antifungal drug restores the effect on drug-resistant fungi. Enzyme activity inhibition experiments show that the IC 50 of HEX for Candida albicans Eno1 (CaEno1) enzyme activity inhibition is about 1 / 30 of the IC 50 of HEX for human Eno1 (hEno1) enzyme activity inhibition. HUVEC and Caco2 cell toxicity experiments of POM-HEX show that the toxicity of POM-HEX with high cell permeability is between that of fluconazole and amphotericin B. It shows that in the human body, HEX still has high selectivity for Candida albicans Eno1, and the therapeutic dose of POM-HEX is tolerable to the human body. Therefore, HEX and / or POM-HEX can be used to prevent and / or treat fungal infection, and HEX and / or POM-HEX can be used as a synergist of existing antifungal drugs and used in combination with existing antifungal drugs. Not only does it solve the shortcomings of existing antifungal drugs, such as large toxic and side effects and poor efficacy, but also provides a new antifungal drug target, and provides a new treatment plan for clinical treatment of IFDs. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 is the time-growth curve of the strain in Example 2 of the present application, wherein Figure 1 a is the time-growth curve of sensitive strain Candida albicans SC5314 in the presence of different concentrations of POM-HEX (2, 4, 8 μg / mL); Figure 1 b is the time-growth curve of sensitive strain Cryptococcus neoformans H99 in the presence of different concentrations of POM-HEX (0.25, 0.5, 1 μg / mL); Figure 1 c is the growth inhibition effect of POM-HEX (0.5, 1, 2 μg / mL) combined with fluconazole (4 μg / mL) on drug-resistant strain Candida albicans 103.

[0024] Figure 2 is the drug sensitivity test result (heat map) of POM-HEX alone or in combination with fluconazole against drug-resistant strains in Example 3 of the present application, wherein, Figure 2 a is the drug sensitivity result heat map of POM-HEX alone against Candida albicans SC5314; Figure 2 b is the drug sensitivity result heat map of POM-HEX alone against Cryptococcus neoformans H99; Figure 2 c is the drug sensitivity result heat map of POM-HEX in combination with fluconazole against drug-resistant Candida albicans 103; Figure 2 d is the drug sensitivity result heat map of POM-HEX in combination with fluconazole against drug-resistant Aspergillus fumigatus 7544.

[0025] Figure 3 is the in vivo efficacy of POM-HEX in Example 4 of the present application - brain and kidney burden of Cryptococcus neoformans H99 infected mouse model.

[0026] Figure 4 is the experimental result graph of HEX on the inhibition of CaEno1 and hEno1 enzyme activity in the present application. DETAILED DESCRIPTION

[0027] In order to make the technical means, creative features, purposes and effects realized by the present application easy to understand, the following examples combined with the drawings specifically describe the application of the compound HEX and / or the compound POM-HEX in the prevention and / or treatment of fungal infection drugs.

[0028] Example 1. The minimum inhibitory concentration of POM-HEX alone against different clinical strains at different concentrations

[0029] Materials and methods

[0030] 1. Reagents:

[0031] POM-HEX: purchased from MedChemExpress Co., Ltd., item number HY131904, purity >98%

[0032] HEX purchased from MedChemExpress Co., Ltd., item number HY-131904A, purity >98%

[0033] Fluconazole: Aladdin Co., Ltd., item number E129360, purity >98%

[0034] Dimethyl sulfoxide: Shanghai Shiyi Biological Technology Co., Ltd.

[0035] Each reagent (POM-HEX, fluconazole) was stored at 4°C. Dimethyl sulfoxide was stored in a cool and dark place.

[0036] 2. Strains:

[0037] 1) Sensitivity Candida including C. albicans SC5314 and 3 clinical strains, C. krusei ATCC4969, C. parapsilosis ATCC90081, C. tropicalis ATCC8915, C. glabrata 537; 2) Cryptococcus including C. neoformans (H99, 443, 444, 445), C. gattii (E566, MW179, D2, D2r); 3) A. fumigatus 7544; 4) Drug-resistant strains: drug-resistant C. albicans 103, super-resistant C. auris. All strains were provided by the Jiang Yuanying research group and identified by morphology and biochemistry.

[0038] The experimental C. albicans and Cryptococcus strains were activated by two generations of streaking on Sabouraud dextrose agar medium (SDA), i.e., the stored strains were taken out from the -80°C freezer, melted at room temperature, and then a small amount of bacterial solution was taken with a inoculation loop and inoculated on SDA plates using a partition streaking method. After 48 h of incubation at 30°C (72 h for Cryptococcus), single colonies of appropriate size were picked up with an inoculation loop and activated by streaking again for 48 h (72 h for Cryptococcus) before use. A. fumigatus was inoculated on SDA slant medium, and the rest of the operations were the same as for Candida.

[0039] 3. Culture solution:

[0040] 1) RPMI 1640 liquid culture solution:

[0041] RPMI1640 (Gibco BRL) 10g, NaHCO32.0g, morpholine propyl sulfonic acid (Sigma) 34.5g (0.165M), dissolved in 900ml of triple distilled water, adjusted to pH 7.0 (25°C) with 1N NaOH, made up to 1000ml with triple distilled water, filtered with a 0.22µm microporous filter to remove bacteria, and stored at 4°C after aliquoting.

[0042] 2) Sabouraud dextrose agar solid culture medium (SDA):

[0043] Proteose peptone 10g, glucose 40g, agar 18g, add 50ml of 2mg / ml chloramphenicol aqueous solution, adjust pH to 7.0, make up to 1000ml with triple distilled water, autoclave (121°C, 15min) and store at 4°C before use.

[0044] 3) YPD culture solution:

[0045] Yeast extract 10g, proteose peptone 20g, glucose 20g, dissolve in 900ml of ultrapure water and make up to 1000ml, autoclave (121°C, 15min) and store at 4°C before use.

[0046] 4. Instruments and equipment:

[0047] Multiskan MK3 type enzyme label detector (Labsystems, Finland product);

[0048] Water-isolated electric heating constant temperature incubator (Shanghai Yijin Medical Instrument Factory);

[0049] THZ-82A table type constant temperature oscillator (Shanghai Yijin Medical Instrument Factory);

[0050] SW-CT-IF type super-clean workbench (Suzhou Antai Air Technology Co., Ltd.);

[0051] 5. POM-HEX and fluconazole stock solution:

[0052] Dissolve POM-HEX and fluconazole with DMSO to make a concentration of 6.4 mg / ml, and store at -20℃ for standby.

[0053] 6. Preparation of bacterial solution:

[0054] The night before the experiment, use a inoculation ring to pick up a single colony of appropriate size from the SDA culture medium to inoculate 1 ml of YPD culture solution, and cultivate at 30℃, 200 rpm for 16 h to make the fungus in the late exponential growth phase. After counting the bacterial solution with a blood cell counting board, adjust the concentration of each bacterial solution to 2×10 3 CFU / ml.

[0055] 7. Preparation of drug sensitivity plate:

[0056] Each strain was taken to a sterile 96-well plate, and 100 µl of RPMI 1640 liquid medium was added to the first hole of each row as a blank control; 50 µl of RPMI 1640 liquid medium and 50 µl of bacterial solution were added to the 12th hole as a positive growth control. 98 µl of RPMI 1640 liquid medium was added to the 2nd hole, and 50 µl of the above freshly prepared bacterial solution was added to the 3rd-11th holes; 2 µl of POM-HEX or 0.64 mg / ml of fluconazole with a mother liquor concentration of 5.12 mg / ml was added to the 2nd hole; and the dilution was multiplied by 2 from the 2nd hole to the 11th hole. 50 µl of bacterial solution was added to each of the 2nd-11th holes. Therefore, the final concentrations of POM-HEX in the 2nd-11th holes of the drug sensitivity plate were 512, 256, 128, 64, 32, 16, 8, 4, 2, and 1 µg / ml, respectively, and the final concentrations of fluconazole in the 2nd-11th holes of the drug sensitivity plate were 64, 32, 16, 8, 4, 2, 1, 0.5, 0.12, and 0.125 µg / ml, respectively, and the DMSO content in each hole was ≤1%. Each drug sensitivity plate was placed in a 30℃ constant temperature incubator for incubation.

[0057] 8. Determination of MIC value:

[0058] The Candida was incubated for 24 h and the Cryptococcus neoformans was incubated for 72 h in a thermostat at 30°C, and the OD value of each well was measured at 630 nm by using an enzyme-labeled analyzer. The lowest concentration of the drug in the well with an OD value decreased by more than 80% compared with the positive control well was the MIC (the drug concentration when 80% of the fungal growth was inhibited).

[0059] The above experiments were operated in parallel for 2 to 3 times, and when the MIC value could be accurately repeated or only differed by one concentration, the higher concentration was accepted as the MIC value; when the MIC value differed by more than two concentrations, the experiment needed to be repeated until the requirement was met.

[0060] The experimental results are shown in Table 1

[0061] Table 1 MIC values (μg / ml) of POM-HEX alone against 20 fungal strains

[0062]

[0063] As shown in Table 1, POM-HEX alone has an antifungal effect and can inhibit drug-resistant Candida. POM-HEX alone has an inhibitory effect on 17 of the 20 strains, with an MIC value of 4 to 128 μg / ml, an MIC value of 8 μg / ml for fluconazole-resistant Candida 103, and an MIC value of 64 μg / ml for super-resistant Candida auris 918. It is suggested that POM-HEX alone has an antifungal activity against standard strains and clinical strains of Candida (C. albicans, C. krusei, C. parapsilosis, C. tropicalis, and C. glabrata) and Cryptococcus (C. neoformans and C. gattii), and also has a good antibacterial effect on drug-resistant strains.

[0064] Example 2. Combined drug sensitivity of POM-HEX and fluconazole against drug-resistant strains

[0065] Materials and methods

[0066] 1. The drugs, strains, materials, and bacterial liquid were prepared as in Example 1.

[0067] 2. Preparation of the drug sensitivity plate:

[0068] Each strain was taken in a sterile 96-well plate, 100 μl of RPMI 1640 liquid medium was added to the first well of each row as a blank control; 50 μl of RPMI 1640 liquid medium and 50 μl of bacterial solution were added to the 12th well as a positive growth control. 98 μl of RPMI 1640 liquid medium was added to the 2nd well, and 50 μl of the above-mentioned freshly prepared bacterial solution was added to the 3rd to 11th wells; 2 μl of fluconazole with a concentration of 0.64 mg / ml was added to the 2nd well, and the concentration was diluted by 2 times from the 2nd to the 11th wells. 50 μl of POM-HEX bacterial solution was added to each of the 2nd to 11th wells. The final concentration of POM-HEX from the first row to the eighth row was 128, 64, 32, 16, 8, 4, 2, and 1 μg / ml, respectively, and the final concentration of fluconazole in the 2nd to 11th wells was 64, 32, 16, 8, 4, 2, 1, 0.5, 0.125, and 0.063 μg / ml, respectively. The DMSO content in each well was ≤1%. Each drug sensitivity plate was placed in a 30°C incubator for static culture.

[0069] 3. The MIC value determination was the same as in Example 1.

[0070] The experimental results are shown in Table 2 and Figure 1

[0071] Table 2 MIC values of POM-HEX combined with fluconazole against different fungi (μg / ml)

[0072]

[0073] Note: FLC represents fluconazole, and FLC / POM-HEX represents the combination of fluconazole and POM-HEX.

[0074] As shown in Table 2, Figure 1 It can be seen that POM-HEX and fluconazole have a synergistic antibacterial effect. After the combination of the two drugs, the MIC value of fluconazole against sensitive strains decreased to ≤0.031-0.5 μg / ml, and the FICI was 0.125-0.375. After the combination of POM-HEX and fluconazole, the drug-resistant C. albicans 103 and A. fumigatus 7544 restored their sensitivity to fluconazole, and the FICI was 0.25-0.375.

[0075] Example 3. Time-growth curve experiment of different clinical fungal strains in the presence of different concentrations of POM-HEX

[0076] 1. The drugs, strains, and materials were the same as in Example 1.

[0077] 2. Preparation of bacterial solution: the night before the experiment, use a loop to pick a single colony of appropriate size from the SDA medium and inoculate it into 1 ml of YPD culture medium, and incubate it at 30°C, 200 rpm for 16 h to make the fungus grow to the late exponential phase. Take the bacterial solution and adjust the concentration of each bacterial solution to OD 600nm = 0.1.

[0078] 3. Take 50 ml of the bacterial solution of C. albicans 103 and divide it into 5 groups. Group 1 contains 10 ml of the bacterial solution as the blank control group, group 2 contains the bacterial solution + fluconazole (the final concentration of fluconazole is 4 μg / ml) as the fluconazole single-drug control group, and groups 3, 4 and 5 are the POM-HEX and fluconazole combination groups with concentrations of 2, 1 and 0.5 μg / ml, respectively, containing the bacterial solution + fluconazole + POM-HEX. Incubate at 30°C with shaking, and take the bacterial solution at 0, 4, 8, 12, 16, 20, 24, 32, 36, 40, 44 and 48 h to measure the OD 600nm values. C. neoformans H99 is taken at 0, 8, 16, 24, 32, 40, 48, 56, 64, 72 h for detection.

[0079] The experimental results are shown in Figure 2

[0080] As can be seen from Figure 2 , 4 and 8 μg / ml POM-HEX alone has a growth inhibitory effect on C. albicans SC5314. 0.5 and 1 μg / ml POM-HEX alone has a growth inhibitory effect on C. neoformans H99. Compared with FLC alone, 2, 1 and 0.5 μg / ml POM-HEX combined with 4 μg / ml FLC can significantly inhibit the growth of fluconazole-resistant C. albicans 103, indicating that POM-HEX combined with fluconazole has antibacterial activity. The time-kill curve further confirms the antifungal activity of POM-HEX alone or in combination with fluconazole.

[0081] Example 4. In vivo efficacy of POM-HEX - organ burden experiment of C. neoformans H99 infected mouse model

[0082] 1. The drugs, strains and materials are the same as in Example 1.

[0083] 2. Preparation of bacterial solution: the night before the experiment, use a loop to pick a single colony of appropriate size from the SDA medium and inoculate it into 1 ml of YPD culture medium, and incubate it at 30°C, 200 rpm for 16 h. Centrifuge the C. neoformans at 5000 r, 1 min to discard the supernatant, resuspend it with PBS, and centrifuge it again as before to wash it twice, then resuspend it with PBS. Count the bacterial solution on a hemocytometer, and then adjust the concentration of the bacterial solution to 5 × 10 6CFU / ml.

[0084] 3. Experiment on bacterial load in mouse brain and lung tissues infected with Cryptococcus neoformans H99: 200 µl of bacterial solution was injected into the tail vein of each mouse to establish a Cryptococcus neoformans H99 infection bacteremia model. Infected mice were randomly divided into three groups (n=8 / group): Model group, POM-HEX group (10 mg / kg), and fluconazole group (10 mg / kg). Two hours after infection, the drug was administered via tail vein. Forty-eight hours later, brain and lung tissues were harvested, ground with steel balls, and 100 µl of the tissue homogenate was diluted 1000-fold and 10000-fold. Each 100 µl of diluted tissue solution was plated onto SDA plates and incubated at 30°C for 72 hours before colony counts were determined.

[0085] The experimental results are shown in Figure 3

[0086] Depend on Figure 3 As can be seen, compared with the control group, the POM-HEX group (10 mg / kg) significantly reduced the bacterial load of Cryptococcus neoformans H99 in brain and lung tissue (P < 0.0001). The POM-HEX group (10 mg / kg) was more effective than the fluconazole group (10 mg / kg) in reducing the bacterial load in brain tissue, but less effective than the fluconazole group in reducing the bacterial load in lung tissue. The bacterial load experiment confirmed that POM-HEX has excellent antifungal activity in vivo.

[0087] Example 5. HEX inhibition experiment on CaEno1 & hEno1 enzyme activity

[0088] 1. Expression and purification of CaEno1 and hEno1

[0089] 2. Drug testing

[0090] D-(+)-2-phosphoglycerate sodium hydrate (2-PG, CAS No. 70195-25-4)

[0091] Imidazole (IMD)

[0092] Magnesium acetate [Mg(Ac)2]

[0093] KCl

[0094] Sodium fluoride (NaF): 100mM ddH2O

[0095] Preparation of reaction buffer: 20mM imidazole (1.36g), 400mM KCl (29.82g), 1mM magnesium acetate (0.214g), pH adjusted to 7.0 with HCl, and ultrapure water added to a final volume of 1L.

[0096] 3. Preparation of Enolase protein sample to be tested: After diluting the protein stock solution with ddH2O, dilute the diluted solution 1 with 240 nM protein solution by 2 times to prepare a series of protein solutions with different concentrations of Enolase (240 nM).

[0097] 4. Blank group: Add 50 μl of reaction solution to a quartz cuvette, then add 25 μl of protein sample with different concentrations of HEX, and make up the volume to 100 μl with ddH2O. The final concentration of HEX is 200, 100, 50, 25, 12.5, 6.25, 3.13, 1.56 and 0 μM. These groups are blank groups (without 2-PG, as shown below) for determining OD 240nm The blank of the instrument, i.e. zero setting, is performed to exclude the influence of compounds and DMSO.

[0098] 5. Experimental group:

[0099] Add each reagent to a quartz cuvette in the following order (the reaction system is 100 μL):

[0100]

[0101] After adding each reagent according to the above table, the final concentration of protein sample is 60 nM, and the final concentration of 2-PG is 1 mM. Incubate at 25 °C for 5 min, and determine OD 240nm at the absorption wavelength.

[0102] Positive control for Enolase inhibitor screening: sodium fluoride (NaF) at 5000, 2500, 1250, 625, 312.5, 156.25, 78.13, 39.06 and 0 μM is used as the positive control. Enolase concentration 30 nM 2-PG concentration 1 mM Reaction time 10 min Reaction temperature 25 °C.

[0103] The experimental results are shown in Figure 4

[0104] From Figure 4 it can be seen that the EC 50 of HEX to CaEno1 and hEno1 is 104.2 ± 9.87 nM and 3503.9 ± 327.31 nM, respectively. The inhibitory strength of HEX to CaEno1 is more than 30 times that of HEX to CaEno1, indicating that HEX has high selectivity to Candida albicans Enolase and small toxic side effects on human body.

[0105] The above experimental results show that HEX / POM-HEX has selective antifungal activity, and the combination with fluconazole can make the drug-resistant strains sensitive to fluconazole again, and therefore can be used as a synergist for antifungal drugs.

[0106] The above embodiments are preferred cases of the present application and are not intended to limit the scope of protection of the present application.

Claims

1. Use of a compound POM-HEX in the preparation of a medicine for preventing and / or treating fungal infection, wherein, the structural formula of the compound POM-HEX is as follows: ， the fungus is: Candida albicans SC5314, 395, 538, Candida glabrata 537, Cryptococcus neoformans H99, Cryptococcus gattii D2; and drug-resistant Candida albicans 103, Aspergillus fumigatus 7544.

2. The use according to claim 1, wherein: wherein the fungus includes standard strains and clinical strains.

3. The use according to claim 1, wherein: wherein, the fungus includes strains resistant or sensitive to fluconazole.

4. The use according to claim 1, wherein: wherein the use is a combination of the compound POM-HEX with at least one of the following antifungal drugs: fluconazole, voriconazole, itraconazole, posaconazole, amphotericin B and its liposome, caspofungin and anidulafungin.

5. The use according to claim 1, wherein: wherein the medicine for preventing and / or treating fungal infection includes the compound POM-HEX and pharmaceutically acceptable salts thereof.

6. The use according to any one of claims 1-5, wherein: wherein the medicine for preventing and / or treating fungal infection includes the compound POM-HEX and a pharmaceutically acceptable carrier or excipient.

7. The use according to claim 6, wherein: wherein the pharmaceutically acceptable carrier or excipient includes one or more of the following: wetting agents, emulsifiers, suspending agents, preservatives, salts affecting osmotic pressure, buffers, flavoring agents or coloring agents.

8. The use according to claim 1, wherein: wherein, the use includes the compound POM-HEX preventing and / or treating fungal infection by improving the selectivity of enolase target, reducing the MIC value, inhibiting fungal growth, inhibiting hyphae formation, inhibiting bud formation of fungal cells, and reducing the load of organs in vivo.

Images