CN-121974843-A - Pinctada spinosa class compound and application thereof

Abstract

The invention belongs to the field of biological pharmacy, and particularly relates to a spinosad compound and application thereof. The spinosad compound is separated from a secondary metabolite of actinomyces sp. Pharmacological activity experiments show that the compound has a moderate inhibition effect on multiple drug-resistant 'ESKAPE' pathogenic bacteria enterococcus faecium, staphylococcus aureus, klebsiella pneumoniae, acinetobacter baumannii and escherichia coli. Therefore, the compound has potential for developing novel antibacterial drugs.

Inventors

• LI BING
• LI ZHENG
• ZHAO MING
• LIU ZHENG
• ZHANG LIPING
• XIE ZEPING
• LI JINGJING
• CAO TIEYAO
• YIN HONGMING

Assignees

• 山东国际生物科技园发展有限公司
• 烟台赛普特检测服务有限公司

Dates

Publication Date

20260505

Application Date

20251231

Claims (10)

1. 1. The spinosad compound is characterized by having a chemical structure as shown in the following formula: 。
2. 2. the spinosad of claim 1, characterized in that it is isolated from a secondary metabolite of the marine actinomyces sp.
3. 3. The spinosad of claim 2, wherein the marine actinomycetes sp.kcb-132 has a preservation number of CGMCC No. 25176, which has been preserved in the China general microbiological culture Collection center.
4. 4. The method for preparing the spinosad compound according to claim 2, which comprises culturing marine actinomyces sp.KCB-132 to obtain fermentation product; and purifying the fermentation product.
5. 5. The method according to claim 4, wherein the culture medium used for culturing Streptomyces sp.KCB-132 is ISP2 culture medium or ISP2 seawater culture medium.
6. 6. The method according to claim 4, wherein the purification comprises chromatographic purification of the fermentation product.
7. 7. A non-therapeutic non-diagnostic use of a spinosad compound as defined in any one of claims 1 to 6 in bacterial inhibition or/and killing.
8. 8. The use according to claim 7, for the preparation of antibacterial drugs.
9. 9. The use according to claim 8, wherein the antibacterial agent is used to combat multi-drug resistant bacterial infections.
10. 10. The use according to claim 9, wherein the multi-drug resistant bacteria is at least one of enterococcus faecium, staphylococcus aureus, klebsiella pneumoniae, acinetobacter baumannii, escherichia coli.

Description

Pinctada spinosa class compound and application thereof Technical Field The invention belongs to the field of biological pharmacy, and particularly relates to a spinosad compound and application thereof. Background Currently, global antibiotic resistance has risen to high risk levels and is still continuously spreading and worsening. In the global burden analysis report of antibiotic resistance published by "lancets" in 2022, 495 thousands of people worldwide were shown to die from antibiotic resistance in 2019. The united kingdom issues a warning in reports of drug-resistant infections, 1000 tens of thousands of deaths from super-resistant bacterial infections being higher than those caused by cancer worldwide every year in 2050. If no new antibiotics are present, more people will die because of antibiotic resistance, and development of new antibiotics is not acceptable. It has been found that metabolites isolated from marine organisms have chemical structural diversity and have a wide range of pharmacological activities, including antibacterial, antiparasitic, enzyme inhibitors, antioxidant, cytotoxic activities, and the like. The marine actinomycetes have rich metabolites and are excellent bacterial sources of natural active substances, and the marine actinomycetes form complex and unique metabolic pathways due to the special habitat of high pressure, high salt and low temperature, so that a plurality of novel compounds with novel structures and obvious activity can be produced, and huge research value and development prospect are shown. The Pincerlike compound (PIERICIDINS) is pyridine alkaloid antibiotics separated from actinomycetes, has wide biological activity and is mainly used for killing insects, resisting bacteria, resisting tumors and the like. The common feature of the structure is a 4-pyridinol core, with a methylated polyketone side chain attached at the C-6 position, which is different from the benzoquinone core structure in coenzyme Q. Since the discovery of spinosad A (Piericidin A) in 1963, nearly 80 members have been reported so far, but studies of this class of compounds against multi-drug resistant "ESKAPE" pathogens have been freshly reported. Therefore, the screening of the spinosad compounds which can cope with multi-drug resistant ESKAPE pathogenic bacteria from marine actinomycetes has important significance. Disclosure of Invention Aiming at the defects in the prior art, the invention provides a spinosad compound and application thereof. The compound is separated from a secondary metabolite of marine actinomycetes, has antibacterial activity and has the potential of developing medicines for treating infection caused by multi-drug resistant bacteria. The specific technical scheme is as follows: the invention aims to provide a spinosad compound which is characterized by having a chemical structure as shown in the following formula: 。 The above compound was isolated from the secondary metabolite of Streptomyces sp.KCB-132, a marine actinomycete designated hydropiericidin B1. The antibacterial activity experiment shows that the compound has moderate inhibitory activity on multi-drug resistant ESKAPE pathogenic bacteria. The marine actinomyces sp.KCB-132 is separated from a Chinese bay submarine sediment, and the preservation number of the marine actinomyces sp.KCB-132 is CGMCC No. 25176, and the marine actinomyces sp.KCB-132 is preserved in the China general microbiological culture Collection center. Further, the preparation method of the spinosad compound comprises culturing marine actinomyces sp.KCB-132, and harvesting fermentation product; and purifying the fermentation product. Still further, the culture medium used for culturing Streptomyces sp.KCB-132 is ISP2 culture medium or seawater ISP2 culture medium, preferably seawater ISP2 culture medium. Specifically, the culturing method comprises streaking and inoculating Streptomyces sp.KCB-132 strain into solid culture medium to culture until spores grow, inoculating spores into liquid culture medium, fermenting and culturing, and collecting fermentation product. Wherein the marine actinomycetes are cultured on a solid medium at 25-28 ℃ for 3-5 days. Wherein the spores are cultured for 7-10 days at 25-28 ℃ in liquid culture. Still further, the purification includes chromatographic purification of the fermentation product. Specifically, the purification method is as follows: Filtering the fermentation product to obtain fermentation liquor and mycelium, adsorbing the fermentation liquor by macroporous adsorption resin column, eluting, concentrating under reduced pressure and extracting with organic solvent to obtain fermentation liquor extract, adding organic solvent into mycelium, ultrasonic extracting to obtain mycelium extract, mixing fermentation liquor and mycelium organic solvent extract, concentrating under reduced pressure to obtain crude extract. Subjecting the crude extract to silica gel column chromatography, eluting with