Preparation method for novel antifungal compound and antifungal application
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A compound, antifungal technology, applied in the field of medicine, can solve the problems of human toxicity and side effects
Active Publication Date: 2017-07-18
NORTHEASTERN UNIV +1
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At present, antifungal drugs are mainly imidazoles (such as ketoconazole) and polyenes (such as amphotericin B), all of which have serious toxic side effects on the human body
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Embodiment 1
[0036] Preparation of new compound I
[0037] 1.1 Seed culture of Streptomyces albolongus.
[0038] Seed medium: 0.4 g of yeast extract, 0.4 g of glucose, 0.5 g of malt extract, 0.1 mL of multivitamins, 1.0 mL of trace elements, and 100 mL of distilled water. Culture conditions: pH 7.2, culture temperature 28 degrees Celsius, culture time 48 hours.
[0039] 1.2 Fermentation of Streptomyces albolongus.
[0040] Fermentation medium: soybean powder 10 g / L, peptone 2 g / L, glucose 20 g / L, soluble starch 5 g / L, yeast extract 2 g / L, sodium chloride 4 g / L, dipotassium hydrogen phosphate 0.5 g / L, magnesium sulfate 0.5 g / L, calcium carbonate 2 g / L, distilled water 70 L. Culture conditions: pH 7.8, culture temperature 28 degrees Celsius, culture time 168 hours.
[0041] 1.3 Extraction.
[0042] The fermentation broth obtained in step (2) was centrifuged, and the supernatant was subjected to column chromatography on XAD-16 macroporous adsorption resin (the volume of the macroporous a...
Embodiment 2
[0051] Embodiment 2: antifungal activity test
[0052] Compound I was dissolved in DMSO, and serially diluted to 9 different concentrations (22.0, 11.0, 5.5, 2.75, 1.38, 0.69, 0.36, 0.18, 0.09 mg / mL). Pathogen conditional pathogenic fungi Candida albicans ATCC MYA-2876, Candida parapsilosis ATCC 22019 and Cryptococcus neoformans ATCC 208821 were inoculated in RPMI-1640 medium (10.4 g L -1 RPMI-1640, 2 g L -1 NaHCO 3 , 34.53 g L -1 MOPs, pH 7.0), the concentration of Candida albicans (C.albicans) and Candida parapsilosis (C. parapsilosis) was 2 × 10 3 cfu / mL, the concentration of Cryptococcus neoformans (C.neoformans) bacterial suspension is 5 × 10 4 cfu / mL. The sample was diluted 10 times with RPMI-1640 medium, and 10 μL of sample and 100 μL of bacterial suspension were added to a 96-well plate. An equal volume of DMSO solution was used as a negative control, and amphotericin B was used as a positive control. The results showed that compound I showed strong inhibitory ...
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Abstract
The invention relates to a preparation method for a novel antifungal compound and an antifungal application. The invention discloses a novel compound with a structure formula I as follows, wherein the novel compound is prepared by separating Streptomyces-albolongus which is used as a source; the chemical name is (1beta, 4beta, 4abeta, 8a alpha)-4,8a-dimethyloctahydronaphthalene-1,4a(2H)-diol; the molecular formula is C12H22O2. The invention also provides a preparation method and an application of the compound. The method provided by the invention comprises the following steps: performing fermenting culture on the strain S.albolongus, and then centrifuging, thereby acquiring a culture solution; absorbing the culture solution by a macroreticular resin column, reducing pressure and concentrating the 95% alcohol eluting part, thereby acquiring a crude extract; treating the crude extract with normal phase silica gel, dextrangel LH-20 and reverse phase silica gel column chromatography, thereby acquiring a monomer compound shown as structure I; and adopting nuclear magnetic resonance spectrum and mass spectrum for identifying the structure as the novel compound. An in vitro antifungal activity research proves that the compound I provided by the invention has obvious inhibiting effect to various pathogenic fungi, including candida albicans, candida parapsilosis and cryptococcus neoformans and is expected to be developed into a novel antifungal drug.
Description
technical field [0001] The invention relates to a compound with antifungal activity, in particular to a new compound with antifungal activity extracted from the fermented liquid of actinomycete Streptomyces albolongus and its application in treating fungal infection, which belongs to the technical field of medicine . Background technique [0002] In recent years, the number of people infected by fungi with low immune function has been increasing, especially the incidence of deep fungal infections has risen sharply, and the research on antifungal drugs has become a hot field. At present, antifungal drugs are mainly imidazoles (such as ketoconazole) and polyenes (such as amphotericin B), all of which have serious side effects on the human body. At the same time, the continuous emergence of clinical drug-resistant pathogenic bacteria makes it urgent to discover new antifungal drugs with high efficiency and low toxicity. [0003] Candida, also known as Candida, is an condition...
Claims
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