Fasamycins compounds, preparation method thereof and application thereof to preparation of antibacterial medicines

Abstract

The invention discloses Fasamycins compounds, a preparation method thereof and the application thereof to preparation of antibacterial medicines. Eight novel Fasamycins compounds are separated and purified from a fermented product of Streptoverticillium morookaense SC1169. In-vitro antibacterial activity testing results show that the Fasamycins compounds have a very strong effect of inhibiting methicillin-sensitive staphylococcus aureus (MSSA), methicillin-resistant staphylococcus aureus (MRSA), vancomycin-sensitive enterococcus faecium (VSE) and vancomycin-resistant enterococcus faecium (VRE). The Fasamycins compounds are novel in structure, especially have significant antibacterial activity for drug-resistant bacteria and have a very high research and development potential. The Fasamycins compounds can be applied as novel antibiotics to the control of the drug-resistant bacteria.

Description

Technical field:

[0001] The invention belongs to the field of biomedicine, and specifically relates to a method for producing Fasamycins compounds by using Streptoverticillium morookaense SC1169 and its application in preparing antibacterial drugs. Background technique:

[0002] In the 1940s, penicillin, which was discovered by Fleming from Penicillium, was the first clinically applied antibiotic, saving the lives of a large number of infected people. Since then, with the in-depth development and research on antibiotics, a large number of new antibiotics have emerged one after another and have been widely used in clinical practice, significantly reducing the mortality rate of pneumonia, tuberculosis, meningitis and other diseases. However, with the large-scale and irrational use of antibiotics, a large number of pathogenic bacteria have developed resistance to existing antibiotics. In 1961, the emergence of resistant Staphylococcus aureus (MRSA) was reported for the first t...

Examples

Embodiment 1

[0025] Streptoverticillium morookaense SC1169 strain was inoculated on PDA solid medium, and cultured at 28° C. in the dark for 10 days for activation. Get an appropriate amount of above-mentioned activated bacterial strains and inoculate them into YMG medium (the preparation method of the YMG medium is: dissolve 4g of glucose, 10g of malt extract, and 4g of yeast extract in 1L of water, and sterilize for subsequent use) , 28° C., 150 rpm, and cultivated under dark conditions for 48 hours to obtain seed liquid. Then the above seed liquid was inoculated on wheat solid medium (50 g of wheat was added to every 50 mL of YMG medium, mixed uniformly and then sterilized), and cultured statically at 28° C. in the dark for 30 days to obtain a solid fermentation culture.

[0026]The solid fermentation culture was leached three times with 95% ethanol by volume fraction, each time for 48 hours. The extract was concentrated under reduced pressure to obtain the extract, which was dissolved...

Embodiment 2

[0043] Embodiment 2: Fasamycins compound antibacterial activity test shown in formula (1)

[0044]Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecium (VSE) and vancomycin-resistant Enterococcus faecium (VRE) were used as test strains, and 25 mL of MHB medium was used at 37 Cultivate on a shaker at 150 rpm for 12 h, adjust the concentration of each bacterial suspension to 1×10 with MHB 5 CFU / mL. Each test sample (compound 1-8) was dissolved in DMSO and diluted to the required concentration, the final concentration of each test sample was: 10, 5, 2.5, 1.25, 0.625 and 0.3125 μg / mL. Set the same concentration of DMSO instead of the test sample as a negative control, Alamar Blue suspension without bacteria as a blank control, and vancomycin as a positive control. Add 100 μL of bacterial suspension containing Alamar Blue (8%, v / v) and diluted test samples (4%, v / v) to a 96-well plate, and each treatment has three replicates, at 37...

Technical field:

[0001] The invention belongs to the field of biomedicine, and specifically relates to a method for producing Fasamycins compounds by using Streptoverticillium morookaense SC1169 and its application in preparing antibacterial drugs. Background technique:

[0002] In the 1940s, penicillin, which was discovered by Fleming from Penicillium, was the first clinically applied antibiotic, saving the lives of a large number of infected people. Since then, with the in-depth development and research on antibiotics, a large number of new antibiotics have emerged one after another and have been widely used in clinical practice, significantly reducing the mortality rate of pneumonia, tuberculosis, meningitis and other diseases. However, with the large-scale and irrational use of antibiotics, a large number of pathogenic bacteria have developed resistance to existing antibiotics. In 1961, the emergence of resistant Staphylococcus aureus (MRSA) was reported for the first t...

Examples

Embodiment 1

[0025] Streptoverticillium morookaense SC1169 strain was inoculated on PDA solid medium, and cultured at 28° C. in the dark for 10 days for activation. Get an appropriate amount of above-mentioned activated bacterial strains and inoculate them into YMG medium (the preparation method of the YMG medium is: dissolve 4g of glucose, 10g of malt extract, and 4g of yeast extract in 1L of water, and sterilize for subsequent use) , 28° C., 150 rpm, and cultivated under dark conditions for 48 hours to obtain seed liquid. Then the above seed liquid was inoculated on wheat solid medium (50 g of wheat was added to every 50 mL of YMG medium, mixed uniformly and then sterilized), and cultured statically at 28° C. in the dark for 30 days to obtain a solid fermentation culture.

[0026]The solid fermentation culture was leached three times with 95% ethanol by volume fraction, each time for 48 hours. The extract was concentrated under reduced pressure to obtain the extract, which was dissolved...

Embodiment 2

[0043] Embodiment 2: Fasamycins compound antibacterial activity test shown in formula (1)

[0044]Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecium (VSE) and vancomycin-resistant Enterococcus faecium (VRE) were used as test strains, and 25 mL of MHB medium was used at 37 Cultivate on a shaker at 150 rpm for 12 h, adjust the concentration of each bacterial suspension to 1×10 with MHB 5 CFU / mL. Each test sample (compound 1-8) was dissolved in DMSO and diluted to the required concentration, the final concentration of each test sample was: 10, 5, 2.5, 1.25, 0.625 and 0.3125 μg / mL. Set the same concentration of DMSO instead of the test sample as a negative control, Alamar Blue suspension without bacteria as a blank control, and vancomycin as a positive control. Add 100 μL of bacterial suspension containing Alamar Blue (8%, v / v) and diluted test samples (4%, v / v) to a 96-well plate, and each treatment has three replicates, at 37...

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