Application of piperazine compounds in the preparation of active products for inhibiting Candida albicans

Abstract

The present invention belongs to the field of medical technology, and provides the use of piperazine compounds in preparing active products for inhibiting Candida albicans. The present invention discloses a new use of a compound of formula I, which is the use of the compound of formula I or a pharmaceutically acceptable salt thereof in preparing active products for inhibiting Candida albicans. The present invention adopts a microplate double dilution method to measure the activity of the compound of formula I in inhibiting Candida albicans, and the results show that the compound of formula I has good antibacterial activity against Candida albicans, and is expected to discover new drugs for treating Candida albicans infection.

Description

Technical Field

[0001] The invention relates to the field of medical technology, and in particular to application of piperazine compounds in preparing active products for inhibiting Candida albicans. Background Art

[0002] Candida albicans is a pathogenic fungus that is widely spread in humans. It usually causes acute, subacute or chronic infections and is one of the most important pathogens of infection today. Candida albicans Hsp90 Higher organisms can produce a protective response to sudden temperature increases and other adverse conditions. Under adverse conditions, Candida albicans synthesizes and secretes a series of proteins that enable the Candida albicans itself to adapt to adverse living environments. These proteins are called heat shock proteins (Hsps). Hsp90 is mainly distributed in the cytoplasm of Candida albicans, and a small part is located in the cell wall. As a molecular chaperone, it can protect and repair cells, participate in cell growth and division, DNA synthesis, gene transcription, translation, as well as the correct folding, transport and membrane localization of proteins.

[0003] Systemic Candida albicans infection is difficult to diagnose at an early stage, and the best time for treatment is often missed. And with the continuous increase of drug-resistant strains and the limitations of antifungal drugs themselves, the trend of Candida albicans infection is also growing significantly. Therefore, in terms of fungal infection treatment, the development of new drugs for the treatment of fungal infection diseases is imminent. Summary of the invention

[0004] The purpose of the present invention is to overcome the defects in the prior art and provide the use of piperazine compounds in the preparation of active products for inhibiting Candida albicans.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] Use of the compound of formula I in the preparation of a product active in inhibiting Candida albicans;

[0007]

[0008] Preferably, the product is a medicine.

[0009] The present invention also provides the use of the compound of formula I in the preparation of active drugs for inhibiting Candida albicans;

[0010]

[0011] Preferably, the medicine is an injection, tablet, powder, granule, capsule, oral solution, ointment or cream.

[0012] The present invention also provides a method for inhibiting the activity of Candida albicans, comprising the following steps: using the prepared product for inhibiting the activity of Candida albicans to mix with Candida albicans for inhibition.

[0013] The present invention also provides a method for inhibiting the activity of Candida albicans, which comprises mixing the prepared drug for inhibiting the activity of Candida albicans with Candida albicans for inhibition.

[0014] The present invention has the following advantages:

[0015] The present invention provides the use of a compound of formula I in the preparation of a product active in inhibiting Candida albicans:

[0016]

[0017] The present invention discloses a new use of a compound shown in formula I, which is the use of the compound shown in formula I or a pharmaceutically acceptable salt thereof in the preparation of a product for inhibiting the activity of Candida albicans, especially a product for inhibiting Candida albicans infection. The present invention adopts a microplate double dilution method to measure the activity of the compound shown in formula I in inhibiting Candida albicans. The results show that the compound shown in formula I has good antibacterial activity against Candida albicans, and is expected to discover new drugs for treating Candida albicans infection. DETAILED DESCRIPTION

[0018] The present invention provides the use of a compound of formula I in preparing a product active in inhibiting Candida albicans;

[0019]

[0020] In the present invention, the CAS number of the compound of formula I is No.94995-85-4.

[0021] In the present invention, the Candida albicans is preferably a Candida albicans sensitive strain and a Candida albicans resistant strain.

[0022] In the present invention, the product is preferably a medicine.

[0023] The present invention also provides an application of a compound of formula I in the preparation of a drug active in inhibiting Candida albicans;

[0024]

[0025] In the present invention, the drug is preferably an injection, tablet, powder, granule, capsule, oral solution, ointment or cream.

[0026] In the present invention, the drug for inhibiting the activity of Candida albicans can also be added with one or more pharmaceutically acceptable carriers.

[0027] In the present invention, the carrier includes conventional diluents, excipients, fillers, binders, wetting agents, disintegrants, absorption promoters, surfactants, adsorption carriers, lubricants, etc. in the pharmaceutical field.

[0028] In the present invention, the provided drug for inhibiting the activity of Rosa albicans can be introduced into the body such as muscle, intradermal, subcutaneous, intravenous, mucosal tissue by injection, spraying, nasal drops, eye drops, penetration, absorption, physical or chemical mediation methods; or introduced into the body after being mixed or wrapped with other substances.

[0029] The present invention also provides a method for inhibiting the activity of Candida albicans, comprising the following steps: mixing the prepared product for inhibiting the activity of Candida albicans with Candida albicans for inhibition.

[0030] In the present invention, the concentration of the product inhibiting Candida albicans cannot be lower than the minimum inhibitory concentration of Candida albicans.

[0031] The present invention also provides a method for inhibiting the activity of Candida albicans, comprising the following steps: mixing the prepared drug for inhibiting the activity of Candida albicans with Candida albicans to inhibit the activity of Candida albicans.

[0032] In the present invention, the concentration of the drug inhibiting Candida albicans cannot be lower than the minimum inhibitory concentration of Candida albicans.

[0033] The present invention also provides the use of the compound of formula I in preparing a Candida albicans antibacterial agent.

[0034] The present invention also provides a Candida albicans inhibitor, which consists of the compound of formula I or a pharmaceutically acceptable salt thereof.

[0035] The present invention also provides the use of the compound of formula I in preparing products for resisting Candida albicans infection.

[0036] The present invention also provides an application in preparing a product for preventing and / or treating diseases caused by Candida albicans infection.

[0037] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0038] Example 1

[0039] The compound of formula I was purchased from Shanghai Taoshu Biotechnology Co., Ltd., item number: F0870-0050.

[0040] RPMI Media 1640: Gibco, USA. Fluconazole and amphotericin B: Sigma-Aldrich, USA.

[0041] 1) Preparation of bacterial culture

[0042] The sensitive strain of Candida albicans (Candida albicans SC5314) and the resistant strain of Candida albicans (C.albicans 17#, C.albicans g5) (Gong Jiao, Wu Ju, Ikeh Melanie, Tao Li, Zhang Yulong, Bing Jian, Nobile Clarissa J., Huang Guanghua. Antifungal 1 Activity of Mammalian Serum amyloid A1 against Candida albicans. Antimicrobial Agents and Chemotherapy. 64(1): e01975-19) were respectively prepared into (2-5)×10 5 cells / mL of bacterial solution.

[0043] 2) Preparation of test compound formula I solution

[0044] Compound I was prepared into a 4 mg / mL stock solution using sterile DMSO as solvent, and then diluted with sterile DMSO in sequence to obtain dilutions with concentrations of 2 mg / mL, 1 mg / mL, 500 μg / mL, 250 μg / mL, 125 μg / mL, 62.5 μg / mL, 31.25 μg / mL, 15.625 μg / mL, 7.81 μg / mL, 3.91 μg / mL, 1.95 μg / mL, and 0.98 μg / mL.

[0045] The positive control drugs (fluconazole and amphotericin B) were prepared in sequence as 320 μg / mL stock solutions using sterile DMSO as solvent, and then diluted in sequence with sterile DMSO to obtain dilutions with concentrations of 160 μg / mL, 80 μg / mL, 40 μg / mL, 20 μg / mL, 10 μg / mL, 5 μg / mL and 2.5 μg / mL as positive control drugs for the detection of Candida albicans.

[0046] 3) Determine the minimum inhibitory concentration of compound I for inhibiting Candida albicans

[0047] a. Take a 96-well cell culture plate and add 40 μL RPMI Media 1640 culture medium to each well.

[0048] b. Take the 96-well cell culture plate that has completed step a and group it as follows:

[0049] Positive control group (7 wells): add 2 μL of the 7 dilutions of the positive control drug prepared in step 2) to each well;

[0050] Experimental group (7 wells for each compound): add 2 μL of the compound dilution prepared in step 2) respectively;

[0051] Negative control group (7 wells): 2 μL of sterile DMSO was added to each well.

[0052] c. Take the 96-well cell culture plate that has completed step b, add 78 μL of the bacterial solution obtained in step 1) to each well, and observe the growth of Candida albicans in each well after culturing at 35°C for 24 hours: if the well is turbid, it means that the compound at the corresponding concentration has no inhibitory activity against Candida albicans; if the well is clear, it means that the compound at the corresponding concentration has inhibitory activity against Candida albicans. For each compound, the final concentration of the compound corresponding to the well where the growth of Candida albicans is completely inhibited (the concentration of the compound solution in the added diluent / 40) is the minimum inhibitory concentration of the compound against Candida albicans, MIC value. The results are shown in Table 1

[0053] Table 1 Antifungal activity test results of compound I (MIC value, μg / ml)

[0054] Formula I Fluconazole Amphotericin B Candida albicans sc5314 3.125 0.39 0.78 Candida albicans 17 6.25 50 0.78 Candida albicans g5 6.25 50 1.56

[0055] As can be seen from the above examples, the present invention provides the use of the compound of formula I in the preparation of a product having an activity of inhibiting Candida albicans. As can be seen from Table 1, the compound of formula I provided by the present invention has an effect of inhibiting the activity of Candida albicans.

[0056] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. Use of the compound of formula I in the preparation of active products for inhibiting Candida albicans; 2. The use according to claim 1, characterized in that: The product described is a drug.

3. The use according to claim 2, characterized in that: The medicine is in the form of injection, tablet, powder, granule, capsule, oral solution, ointment or cream.

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