Application of benzothiazole compound in preparing products for inhibiting Candida albicans

Abstract

The present invention belongs to the field of pharmaceutical technology and provides the use of the compound of formula I in the preparation of a product for inhibiting the activity of Candida albicans. The present invention discloses the use of the compound of formula I in the preparation of a product for inhibiting the activity of Candida albicans. The present invention uses the microplate two-fold dilution method to determine the inhibitory activity of the compound of formula I against Candida albicans. The results show that the compound of formula I has good antibacterial activity against Candida albicans and is expected to discover new drugs for the treatment of Candida albicans infections.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and particularly to the application of benzothiazole compounds in the preparation of products for inhibiting Candida albicans. Background Art

[0002] Over time, the drug resistance of pathogenic fungi has gradually increased, but antifungal drugs for treating deep fungal infections are still very scarce. At the same time, existing drugs may cause corresponding side effects. For example, fluconazole is a common antifungal drug, but it has a limited antibacterial spectrum, is not effective against drug-resistant strains, and can cause drug interactions, which are harmful to the human body. Caspofungin, an antifungal drug that acts on the fungal cell wall β-1,3-glucan synthase, has a complex structure, is difficult to produce, and also has hemolytic toxicity. Therefore, there is an urgent need for a new antifungal drug to solve the current problem of fungal infections, which is very important for the development of medicine.

[0003] Candida albicans is a single-celled fungus with a round or oval-shaped cell body, 3-6 μm in diameter, gram-positive staining, uneven coloring, and reproduces by budding. It is easy to form blastospores and pseudohyphae in tissues. Blastospores are mostly concentrated at the connection sites of pseudohyphae, and there are often larger, thin-walled round or pear-shaped chlamydospores in the middle or at the top of the pseudohyphae, which is one of the characteristics of Candida albicans. It is often present in the mucosal parts of the human body such as the oral cavity, upper respiratory tract, intestine, and vagina. When the body shows dysbacteriosis, especially when the immunity decreases, it can cause candidiasis. Recently, due to the increased use of antibacterial drugs, hormones, and immunosuppressants, the trend of Candida albicans infection has also increased significantly. Summary of the Invention

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

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

[0006] The present invention provides the application of the compound of formula I in the preparation of products with Candida albicans inhibitory activity;

[0007]

[0008] Preferably, the product is a drug.

[0009] The present invention also provides the application of the compound of formula I in the preparation of drugs with Candida albicans inhibitory activity;

[0010]

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

[0012] The present invention also provides a method for inhibiting Candida albicans, comprising the following steps: mixing a product that inhibits the activity of Candida albicans with Candida albicans for inhibition.

[0013] The present invention also provides a method for inhibiting Candida albicans, comprising the following steps: mixing a drug that inhibits 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 the compound of formula I in the preparation of a product for inhibiting the activity of Candida albicans;

[0016]

[0017] The present invention discloses the use of the compound of formula I in the preparation of a product for inhibiting the activity of Candida albicans, especially in the preparation of a product for inhibiting Candida albicans infection. The present invention uses the microplate two-fold dilution method to determine the activity of the compound of formula I against Candida albicans. The results show that the compound shown in formula I has good antibacterial activity against Candida albicans, and it is expected to discover new drugs for the treatment of Candida albicans infection. Detailed implementation manners

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

[0019]

[0020] In the present invention, the CAS number of the compound of formula I is: No. 381200-04-0.

[0021] In the present invention, the Candida albicans includes Candida albicans sensitive strains and Candida albicans drug-resistant strains.

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

[0023] The present invention also provides the use of the compound of formula I in the preparation of a drug for inhibiting the activity of Candida albicans;

[0024]

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

[0026] In the present invention, the above-mentioned drugs can be introduced into the body such as muscle, intradermal, subcutaneous, intravenous, mucosal tissues by injection, spraying, nasal dropping, eye dropping, penetration, absorption, physical or chemical mediated methods; or be introduced into the body after being mixed or encapsulated with other substances.

[0027] In the present invention, when needed, one or more pharmaceutically acceptable carriers may be added to the above-mentioned drug.

[0028] The carriers in the present invention include conventional diluents, excipients, fillers, binders, wetting agents, disintegrants, absorption promoters, surfactants, adsorption carriers, lubricants, etc. in the pharmaceutical field.

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

[0030] In the present invention, the minimum use concentration of the product with inhibitory activity against Candida albicans cannot be lower than the minimum inhibitory concentration of the fungus it inhibits.

[0031] The present invention also provides a method for inhibiting Candida albicans, comprising the following steps: mixing a drug with inhibitory activity against Candida albicans with Candida albicans for inhibition.

[0032] In the present invention, the minimum use concentration of the drug with inhibitory activity against Candida albicans cannot be lower than the minimum inhibitory concentration of the fungus it inhibits.

[0033] The present invention also provides the use of the compound of formula I in the preparation of an inhibitor of Candida albicans.

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

[0035] The present invention also provides the use of the compound of formula I in the preparation of a product for anti-Candida albicans infection.

[0036] The present invention also provides the use of the compound of formula I in the preparation of 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 examples, 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 TargetMol Co., Ltd., product number: F0853-0210.

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

[0041] 1) Preparation of bacterial solution

[0042] Count by hemocytometer, and use RPMI Media 1640 medium to prepare suspensions of Candida albicans sensitive strain (Candida albicans SC5314), Candida albicans drug-resistant strains (C. albicans 17#, C. albicans g5) (GongJiao, Wu Ju, Ikeh Melanie, Tao Li, ZhangYulong, Bing Jian, Nobile Clarissa J., HuangGuanghua. Antifungal 1Activity of Mammalian Serum amyloid A1 against Candida albicans. Antimicrobial Agents and Chemotherapy. 64(1):e01975-19) to a cell density of (2-5)×10 5 cells / mL.

[0043] 2) Prepare the test compound solution of Formula I

[0044] Using sterile DMSO as a solvent, prepare a stock solution of the compound of Formula I at 4 mg / mL, and then serially dilute it with sterile DMSO to obtain dilution solutions 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] Using sterile DMSO as a solvent, prepare a stock solution of the positive control drug (fluconazole) at 320 μg / mL, and then serially dilute it with sterile DMSO to obtain dilution solutions 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 the positive control drug for the detection of Candida albicans.

[0046] 3) Determine the minimum inhibitory concentration of the compound of Formula I against Candida albicans

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

[0048] b. Take the 96-well cell culture plate completed in step a and perform the following grouping treatments:

[0049] Positive control group (7 wells): Add 2 μL of the 7 dilution solutions of the positive control drug prepared in step 2) respectively;

[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): Add 2 μL of sterile DMSO respectively.

[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 status of Candida albicans in each well after culturing at 35 °C for 24 hours: If the well is turbid, it indicates that the compound at the corresponding concentration has no inhibitory activity against Candida albicans; if the well is clear, it indicates 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 dilution / 40) is the minimum inhibitory concentration (MIC value) of the compound against Candida albicans. The results are shown in Table 1

[0053] Table 1 Results of the detection of the inhibitory activity of the compound of formula I against Candida albicans (MIC value, μg / ml)

[0054] Formula I Fluconazole Candida albicans sc5314 0.78 0.39 Candida albicans 17 1.56 50 Candida albicans g5 1.56 100

[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 for inhibiting the activity of Candida albicans. As can be seen from Table 1, the compound of formula I provided by the present invention has an effect of inhibiting Candida albicans.

[0056] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. Use of the compound of formula I in the preparation of a product for inhibiting the activity of Candida albicans; Formula I.

2. Use of the compound of formula I in the preparation of a drug for inhibiting the activity of Candida albicans; Formula I.

3. The application according to claim 2, wherein The drug is an injection, tablet, powder, granule, capsule, oral liquid, ointment, or cream.

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