CN-121991016-A - Coumarin compound and preparation method and application thereof

Abstract

The invention relates to a coumarin compound and application thereof, in particular to a coumarin compound, a preparation method and application thereof, wherein the coumarin compound is 3,3' - (4-iodobenzylidene) -bis-4-hydroxycoumarin, and the structural formula of the coumarin compound is shown as formula I. The 3,3' - (4-iodobenzylidene) -bis-4-hydroxycoumarin in the technical scheme of the invention is a novel compound which is not researched, can accurately target periodontal critical pathogenic microorganisms including porphyromonas gingivalis, actinomyces viscosus, actinomyces naeslundii, gordon streptococcus and the like at a lower concentration, and fills the blank that the prior art does not report to selectively inhibit the activity of periodontal pathogenic bacteria.

Inventors

• KONG HUI
• ZHU QINGLIN
• LI MINGKAI
• XIN JIAJIA
• LIU XIANGDONG
• CHEN HONGWEI
• GUO QIAN

Assignees

• 中国人民解放军空军军医大学

Dates

Publication Date

20260508

Application Date

20260319

Claims (10)

1. 1. The coumarin compound is 3,3' - (4-iodobenzylidene) -bis-4-hydroxycoumarin, and has a structural formula shown in formula I; Formula I.
2. 2. The preparation method of the coumarin compound is characterized by comprising the specific steps of reacting 4-hydroxycoumarin with 4-iodobenzaldehyde by taking absolute ethyl alcohol as a solvent to obtain 3,3' - (4-iodobenzylidene) -bis-4-hydroxycoumarin, wherein the mass ratio of the 4-hydroxycoumarin to the 4-iodobenzaldehyde is 1.4-2.2:1.
3. 3. The use of a coumarin compound according to claim 1 in the manufacture of a medicament for the treatment of periodontitis.
4. 4. The use according to claim 3, wherein the coumarin compound has antibacterial activity against one or more of the following periodontal disease-causing pathogens; The periodontal disease-causing pathogens include Porphyromonas gingivalis (Porphyromonas gingivalis), actinomyces viscosus (Actinomyces Viscosus), actinomyces naeslundii (Actinomyces naeslundii), and Streptococcus gordonii (Streptococcus gordonii).
5. 5. The use according to claim 4, wherein the coumarin compound has a minimum inhibitory concentration of 2 μg/mL for porphyromonas gingivalis, 16 μg/mL for actinomyces viscosus, 16 μg/mL for actinomyces naeslundii and 8 μg/mL for streptococcus gordoniae.
6. 6. The use according to claim 3, wherein said medicament comprises said 3,3' - (4-iodobenzylidene) -bis-4-hydroxycoumarin as an active ingredient.
7. 7. The use according to claim 6, wherein the effective concentration of 3,3' - (4-iodobenzylidene) -bis-4-hydroxycoumarin in the medicament is 2 μg/mL to 16 μg/mL.
8. 8. The use of claim 6, wherein the medicament further comprises a pharmaceutically acceptable carrier.
9. 9. The use according to claim 7, wherein the pharmaceutically acceptable carrier comprises any one or more of dimethyl sulfoxide, glycerol, lecithin and cholesterol.
10. 10. Use according to claim 3, wherein the pharmaceutical dosage form is selected from the group consisting of oral dosage form, injection dosage form, inhalation dosage form, topical sustained release formulation, topical rinse, topical gargle or topical spread gel.

Description

Coumarin compound and preparation method and application thereof Technical Field The invention relates to a coumarin compound and application thereof, in particular to a coumarin compound and a preparation method and application thereof. Background Periodontitis is a chronic inflammatory disease caused by plaque biofilm and is characterized by progressive destruction of periodontal support tissues, including gums, periodontal membranes, alveolar bone, and cementum. It is one of the main causes of tooth loss in adults and is closely related to various systemic diseases such as cardiovascular diseases, diabetes, respiratory diseases, etc. Currently, the treatment of periodontitis mainly relies on mechanical debridement, such as subgingival scraping and root surface flattening, supplemented with antibiotics or antiseptics, such as metronidazole, doxycycline, minocycline, chlorhexidine, etc. However, the existing treatment scheme has the remarkable limitations that 1, the existing treatment scheme is poor in targeting, most of traditional antibiotics are broad-spectrum antibacterial, have synergistic pathogenic key flora on porphyromonas gingivalis, actinomyces viscosus, actinomyces naeslundii and the like, and lack of targeted inhibition effect, so that pathogens are not thoroughly removed, 2, the biological membrane is not thoroughly removed, the dental plaque biological membrane is compact in structure, the biological membrane in deep periodontal pockets is difficult to be completely removed by physical debridement, the antibiotics are difficult to permeate into the biological membrane, the internal 'stay bacteria' cannot be effectively killed, and 3, the antibacterial agent often accompanies cytotoxicity under the effective concentration, so that the local application safety is influenced. When reaching the effective antibacterial concentration, many antibacterial drugs have obvious toxicity to host cells such as gingival fibroblasts, immune cells and the like, limit the safety of long-term or high-concentration local use of the antibacterial drugs and are not beneficial to the restoration of periodontal tissues. In summary, development of a new drug capable of achieving high-efficiency bacteriostasis, good biological membrane penetrability and safety is needed to improve the curative effect and safety of periodontitis treatment. Disclosure of Invention In order to solve the problems, the invention provides a coumarin compound, and a preparation method and application thereof. The invention is realized by the following technical scheme: The coumarin compound is 3,3' - (4-iodobenzylidene) -bis-4-hydroxycoumarin, and has a structural formula shown in formula I. Formula I. The preparation method of the coumarin compound comprises the specific steps of reacting 4-hydroxycoumarin with 4-iodobenzaldehyde by taking absolute ethyl alcohol as a solvent to obtain 3,3' - (4-iodobenzylidene) -bis-4-hydroxycoumarin, wherein the mass ratio of the 4-hydroxycoumarin to the 4-iodobenzaldehyde is 1.4-2.2:1. The coumarin compound is applied to the preparation of medicines for treating periodontitis. Preferably, the coumarin compound has antibacterial activity against one or more of the following periodontal disease-causing pathogens; The periodontal disease-causing pathogens include Porphyromonas gingivalis (Porphyromonas gingivalis), actinomyces viscosus (Actinomyces Viscosus), actinomyces naeslundii (Actinomyces naeslundii), and Streptococcus gordonii (Streptococcus gordonii). Preferably, the coumarin compound has a minimum inhibitory concentration of 2 mug/mL for Porphyromonas gingivalis, 16 mug/mL for Actinomyces viscosus, 16 mug/mL for Actinomyces naeslundii and 8 mug/mL for Streptococcus gordonii. Preferably, the medicament takes the 3,3' - (4-iodobenzylidene) -bis-4-hydroxycoumarin as an active ingredient. Preferably, the effective concentration of 3,3' - (4-iodobenzylidene) -bis-4-hydroxycoumarin in the medicament is 2-16 mug/mL. Preferably, the medicament further comprises a pharmaceutically acceptable carrier. Preferably, the pharmaceutically acceptable carrier comprises any one or more of dimethyl sulfoxide, glycerol, lecithin and cholesterol. Preferably, the pharmaceutical dosage form is selected from the group consisting of oral dosage forms, injectable dosage forms, inhaled dosage forms, topical sustained release formulations, topical rinses, topical gargles, and topical spread gels. Preferably, the local sustained and controlled release preparation is prepared by wrapping the 3,3' - (4-iodobenzylidene) -bis-4-hydroxycoumarin in biodegradable polymer fibers, gels or chips. Compared with the prior art, the invention has the following beneficial effects: The invention provides a coumarin compound, which is 3,3' - (4-iodobenzylidene) -bis-4-hydroxycoumarin, and the structural formula of the coumarin compound is shown as formula I. The compound provided by the invention is an unreveyed novel compound, can accurately