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Application of CC-115 in preparation of antifungal drug and pharmaceutical composition thereof

A CC-115, 1. CC-115 technology, applied in the field of medicine, can solve the problems such as the antifungal effect of CC-115 compounds, which is not seen, and achieve the effects of improving the antifungal effect, saving medical expenses, and reducing toxic and side effects

Active Publication Date: 2019-11-05
SHAANXI UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There is no report on the antifungal effect of CC-115 compound at home and abroad, and there is no report on the combined use of antifungal azoles in the treatment of fungal infections

Method used

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  • Application of CC-115 in preparation of antifungal drug and pharmaceutical composition thereof
  • Application of CC-115 in preparation of antifungal drug and pharmaceutical composition thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] The effect of embodiment 1 compound CC-115 used alone on different fungi

[0021] Materials and methods

[0022] 1. Test drug:

[0023] Compound CC-115 (CAS: 1228013-15-7): purchased from Shanghai Danquan Pharmaceutical Technology Co., Ltd., purity ≥ 99%.

[0024] Fluconazole: sigma company, batch number 036M4709V.

[0025] Dimethylsulfoxide (DMSO): Tianjin Tianli Chemical Reagent Co., Ltd.

[0026] Each reagent was prepared in DMSO and stored at -20°C. Before the experiment, the drug was taken out and placed in a 35°C incubator to melt, and mixed thoroughly.

[0027] 2. Strains:

[0028] Strains used: including 1) sensitive strains: sensitive Candida albicans (SC5314), Candida parapsilosis (22019), Cryptococcus neoformans (32609); 2) drug-resistant strains: drug-resistant Candida albicans (103), drug-resistant Tropical Candida, naturally resistant Candida krusei (ATCC2340), naturally resistant Candida glabrata (ATCC2281). The strains were all donated to the rese...

Embodiment 2

[0053] Example 2. Effect of compound CC-115 combined with fluconazole on fungi

[0054] 1, medicine, bacterial strain, material are with embodiment 1

[0055] 2. Experimental procedure: Take a piece of sterile 96-well plate, add 100 μL of RPMI 1640 liquid culture medium to No. 1 well of each row as a blank control; add the above-mentioned freshly prepared drug-resistant Candida albicans bacteria solution (1 ×10 3 ~5×10 3 CFU / mL) 100 μL; No. 2 well was added with 200 μL of bacterial solution; No. 12 well did not contain drugs, and only 100 μL of bacterial solution was added as a positive growth control. The final drug concentrations of fluconazole in each well were 64, 32, 16, 8, 4, 2, 1, 0.5, 0.25 and 0.125 μg / mL, and the combined CC-115 drug concentrations were 16, 8, 4, 2 , 1 μg / mL, the drug concentrations for single use were 64, 32, 16, 8, 4, 2, 1, 0.5, 0.25 and 0.125 μg / mL. The DMSO content in each well was lower than 1%. The 96-well plate was incubated in a 35°C incu...

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Abstract

The invention relates to the technical field of medicines and provides application of CC-115 in preparation of an antifungal drug and a pharmaceutical composition thereof. In vitro experiments show that the compound CC-115 has a good inhibitory effect on fungi and can recover the effect of an antifungal drug fluconazole on drug resistance fungi. Thereby, the compound CC-115 can be used as an antifungal drug and a synergist of the antifungal drug. The invention opens up a new way for the compound CC-115. The compound CC-115 is used as the antifungal drug and the synergist of the antifungal drug, providing a new lead compound or a candidate drug for the antifungal therapy and enhancing antifungal effect of existing drugs. Under the circumstance that clinic antifungal resistance is becoming increasingly widespread and drug resistance is on the rise, the CC-115 recovers the effect of an antifungal drug on drug resistance fungi and reduces dosage of an antifungal drug, thus saving medical expenses for patients and reducing toxic and side effect of drugs.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to the application of CC-115 in the preparation of antifungal drugs and its pharmaceutical composition. Background technique [0002] Compound 1-ethyl-7-[2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl]-3,4-dihydropyrazino[2 ,3-b]pyrazin-2(1H)-one (commonly known as CC-115) is a potent mammalian target of rapamycin (mTOR) and DNA-dependent protein kinase (DNA Dependent proteinkinase, DNA-PK) dual inhibitors. Modern pharmacological studies have shown that the compound can treat or prevent cancer, inflammatory diseases, immune diseases, neurodegenerative diseases, diabetes, obesity, nervous system diseases, age-related diseases or cardiovascular diseases. There is no report on the antifungal effect of CC-115 compound at home and abroad, and there is no report on the combined use of CC-115 with antifungal azoles in the treatment of fungal infections. Contents of the inve...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4985A61K31/4196A61P31/10
CPCA61K31/4985A61K31/4196A61P31/10A61K2300/00
Inventor 刘伟温芝潼陆琪王胜正
Owner SHAANXI UNIV OF SCI & TECH