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CN-121971420-A - Application of naphthoquinone derivative in preparation of helicobacter pylori resistant medicines

CN121971420ACN 121971420 ACN121971420 ACN 121971420ACN-121971420-A

Abstract

An application of naphthoquinone derivative in preparing anti-helicobacter pylori medicine is provided. The compound is 2-amino-3-chloro-1, 4-naphthoquinone (ACNQ), has strong inhibitory activity on helicobacter pylori standard strain and clinically separated various drug-resistant strains, has the lowest inhibitory concentration range of 0.0625-0.25 mug/mL, and is not easy to induce bacterial drug resistance. The lowest sterilization concentration of ACNQ is 0.125 mug/mL, the sterilization rate reaches 99.99% within 24 hours, and in different pH culture conditions, the sterilization rate of 0.25 mug/mL of ACNQ reaches 99.99% within 4 hours. In vitro cytotoxicity experiments and in vivo safety evaluation of mice prove that the compound has lower toxicity in an effective concentration range. ACNQ provides a new option for the development of novel anti-helicobacter pylori agents, particularly agents directed against drug-resistant strain infections.

Inventors

  • HUANG YANQIANG
  • YANG GUIYAN
  • Luo Jiazi
  • HUANG LINGLI

Assignees

  • 右江民族医学院

Dates

Publication Date
20260505
Application Date
20251218

Claims (8)

  1. 1. Use of 2-amino-3-chloro-1, 4-naphthoquinone in the manufacture of a medicament for inhibiting helicobacter pylori.
  2. 2. The use according to claim 1, wherein the minimum inhibitory concentration of the medicament for inhibiting helicobacter pylori is 0.0625 μg/mL to 0.25 μg/mL and the minimum bactericidal concentration is 0.125 μg/mL.
  3. 3. The use according to claim 1, wherein the unit dosage of 2-amino-3-chloro-1, 4-naphthoquinone in the medicament corresponds to an administration dose of 7 mg/kg to 28 mg/kg.
  4. 4. The use according to claim 1, wherein the helicobacter pylori is a drug resistant helicobacter pylori strain.
  5. 5. The use according to claim 1, wherein the resistant helicobacter pylori strain is resistant to at least one antibiotic selected from the group consisting of metronidazole, clarithromycin, levofloxacin and amoxicillin.
  6. 6. The use according to claim 1, characterized in that the purity of the 2-amino-3-chloro-1, 4-naphthoquinone is greater than 98%.
  7. 7. The use according to claim 1, wherein the medicament is for the treatment of gastritis associated with helicobacter pylori infection.
  8. 8. The use according to claim 1, wherein the medicament is formulated as a solid or liquid formulation for oral administration.

Description

Application of naphthoquinone derivative in preparation of helicobacter pylori resistant medicines Technical Field The invention belongs to the field of medical biology, and in particular relates to a pharmaceutical application of 2-amino-3-chloro-1, 4-naphthoquinone in resisting helicobacter pylori. Background Helicobacter pylori (Helicobacter pylori, hp) is a gram-negative bacterium that survives the strong acid environment in the stomach, and its infection is closely related to chronic gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue lymphoma, and other diseases. Long-term infection can also significantly increase the risk of gastric cancer onset, and is therefore classified as a class I carcinogen by the world health organization. It is counted that about 75% of gastric cancer cases worldwide are associated with helicobacter pylori infection. The strain has the characteristics of high infection rate, high drug resistance rate, high clinical eradication difficulty and the like. The infection rate of helicobacter pylori is obviously different in different countries and regions, the infection rate of developing countries is generally higher than that of developed countries, and the infection rate of low and medium income countries and partial vulnerable groups can be up to more than 75%. The infection rate of helicobacter pylori of adults in China is about 50%, and the prevention and control situation is serious. Currently, the clinic is mainly adopting triple or quadruple therapy comprising two or three antibiotics combined with proton pump inhibitor and/or bismuth agent. However, with the widespread use of antibiotics, the problem of resistance to helicobacter pylori is increasingly prominent, and particularly, the drug resistance rate to common drugs such as metronidazole, clarithromycin, and levofloxacin is continuously rising, resulting in an increase in the failure rate of treatment, and satisfactory eradication effect is difficult to achieve by monotherapy (eradication rate >80% becomes a clinical challenge). Therefore, the search for novel anti-helicobacter pylori drugs, in particular compounds with a new structure, a new mechanism or high selectivity, is the focus of current research. Quinone compounds are a natural product widely existing in plants and are key active ingredients of various medicinal plants. Studies have shown that partial quinone compounds such as emodin, shikonin, juglone, menaquinone and the like have certain helicobacter pylori resisting biological activity. The potential of 2-amino-3-chloro-1, 4-naphthoquinone as a synthetic quinone compound with 1, 4-naphthoquinone as a parent nucleus has been primarily reported in terms of antimalarial and antitumor, but the studies on the antibacterial field, particularly on helicobacter pylori, are still limited. The literature suggests that natural or synthetic compounds containing 1, 4-naphthoquinone backbones often have antimicrobial potential, where the position of the halogen substituent has a significant impact on their antimicrobial activity and selectivity. For example, the introduction of chlorine atoms at the C2 or C3 position generally contributes to the enhancement of the antibacterial and antifungal effects, while heteroatoms such as nitrogen, oxygen, etc., attached to the benzene ring can modulate their redox properties and thus affect the biological activity. Although several naphthoquinone derivatives have shown antibacterial effect, whether 2-amino-3-chloro-1, 4-naphthoquinone has specific inhibition effect on helicobacter pylori and potential thereof in drug-resistant strain infection treatment have not been systematically studied and reported. Disclosure of Invention Aiming at the technical problems, the invention provides the pharmaceutical application of the 2-amino-3-chloro-1, 4-naphthoquinone, namely the anti-helicobacter pylori effect, has good inhibiting effect on sensitive or drug-resistant helicobacter pylori, and can play a role in bacteriostasis and sterilization at low dosage. The technical proposal is that the 2-amino-3-chloro-1, 4-naphthoquinone is applied to the preparation of the medicine for inhibiting helicobacter pylori. Preferably, the minimum inhibitory concentration of the above-mentioned drug for inhibiting helicobacter pylori is 0.0625 μg/mL to 0.25 μg/mL, and the minimum bactericidal concentration is 0.125 μg/mL. Preferably, the unit dosage of 2-amino-3-chloro-1, 4-naphthoquinone in the above-mentioned medicine corresponds to an administration dose of 7 mg/kg to 28 mg/kg. The helicobacter pylori is drug-resistant helicobacter pylori strain. The above-mentioned drug-resistant helicobacter pylori strain is resistant to at least one antibiotic selected from metronidazole, clarithromycin, levofloxacin and amoxicillin. The purity of the 2-amino-3-chloro-1, 4-naphthoquinone is more than 98%. The medicine can be used for treating gastritis associated with helicobacter pylori infection.