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CN-121971438-A - Application of NSC348884 in resisting mycobacterium tuberculosis infection

CN121971438ACN 121971438 ACN121971438 ACN 121971438ACN-121971438-A

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to application of a compound NSC348884 in preparation of anti-mycobacterium tuberculosis medicines. Experimental results show that NSC348884 shows remarkable in vitro antibacterial activity on standard strains and clinical isolates of mycobacterium tuberculosis. The MIC for the standard strain was 2. Mu.g/mL, and the MIC distribution for the clinical isolate was 0.5-4. Mu.g/mL. Further antibacterial activity evaluation shows that after 3 days of treatment with NSC348884 (1. Mu.g/mL), the growth of Mycobacterium tuberculosis is significantly inhibited with an inhibition rate of 41.82% + -10.14%. CFU was reduced by about 0.24 log compared to DMSO control. The findings suggest that NSC348884 has potential for development as a novel antitubercular drug.

Inventors

  • LIU TAO
  • JI YUANFEI
  • LIU WEI
  • YU XIA
  • HUANG HAIRONG

Assignees

  • 首都医科大学附属北京胸科医院
  • 北京市结核病胸部肿瘤研究所

Dates

Publication Date
20260505
Application Date
20251226

Claims (10)

  1. Use of nsc348884 in the preparation of a product for inhibiting mycobacterium tuberculosis.
  2. 2. The use according to claim 1, wherein the mycobacterium tuberculosis comprises mycobacterium tuberculosis carried by a standard strain of mycobacterium tuberculosis, a clinical isolate of mycobacterium tuberculosis or a patient infected with mycobacterium tuberculosis.
  3. 3. The use as claimed in claim 1, wherein the mycobacterium tuberculosis inhibiting product comprises a medical product or a non-medical product, wherein the medical product is a drug or a pharmaceutical adjuvant, and the non-medical product is a bacteriostatic agent.
  4. Use of NSC348884 in the manufacture of a medicament for the prevention and/or treatment of a disease caused by a mycobacterium tuberculosis infection, said NSC348884 acting by inhibiting the activity of mycobacterium tuberculosis.
  5. 5. The use according to claim 4, wherein the mycobacterium tuberculosis comprises mycobacterium tuberculosis carried by a standard strain of mycobacterium tuberculosis, a clinical isolate of mycobacterium tuberculosis or a patient infected with mycobacterium tuberculosis.
  6. 6. The use according to claim 4, wherein the medicament comprises one or more pharmaceutically acceptable carriers.
  7. 7. The use according to claim 4, wherein the pharmaceutical dosage form comprises a tablet, capsule, aerosol, pill, powder, solution, suspension, granule, transdermal agent and/or suppository.
  8. 8. A pharmaceutical composition comprising NSC348884 and another drug against mycobacterium tuberculosis infection, the pharmaceutical composition having at least one of the following efficacy: a) Inhibiting mycobacterium tuberculosis activity; b) Anti-mycobacterium tuberculosis infection; c) Preventing and/or treating diseases caused by mycobacterium tuberculosis.
  9. 9. The pharmaceutical composition of claim 8, wherein the other anti-mycobacterium tuberculosis infection agent comprises one or more of an antibiotic and other agents that can facilitate inhibition or killing of mycobacterium tuberculosis or provide patient resistance.
  10. 10. The pharmaceutical composition of claim 8, wherein the antibiotic comprises one or more of rifampin, streptomycin, ethambutol, moxifloxacin, clarithromycin, and/or amikacin, and the additional drug comprises one or more of vitamins, amino acids, proteins, and/or minerals.

Description

Application of NSC348884 in resisting mycobacterium tuberculosis infection Technical Field The invention belongs to the technical field of biological medicine, and particularly relates to application of NSC 348884. Background Tuberculosis is an infectious disease caused by a complex of mycobacterium tuberculosis (Mycobacterium tuberculosis complex, MTBC), wherein mycobacterium tuberculosis (Mycobacterium tuberculosis, m.tb) is the main pathogen that causes the disease. Although traditional drugs such as rifampicin and isoniazid play a key role in prevention and control by directly targeting mycobacterium tuberculosis, pathogens can generate drug resistance through adaptive evolution under the pressure of the drugs, and limitations of traditional treatment strategies are exposed. Compared with the conventional tuberculosis treatment, the treatment scheme of drug-resistant tuberculosis is more complex, and has longer period, higher toxicity and higher cost （Lyu M Y, Lai H L, Peng H R, et al. Immunotherapy for tuberculosis: current strategies and future directions[J]. Military Medical Research, 2025, 12(1): 68.）. In recent years, new antitubercular drugs and treatment regimens have been developed successively, and the therapeutic effect of patients suffering from multi-drug and wide-drug resistant tuberculosis has been improved and the course of treatment has been shortened (Bi Kefan, cao Dan, ding Cheng, etc. the medical treatment of tuberculosis has been performed in the past, current and future, university of Zhejiang, medical edition, 2022,51 (6): 657-668). However, the antitubercular drugs in western medicines are still limited, development of new drugs is slow, candidate drugs are scarce, the curative effect of the drugs currently in clinical trial stage is still to be further verified （Stephanie F,Saragih M,Tambunan USF,Recent Progregsand Challenges for Drug-Resistant Tuberculosis Treatment. Pharmaceutics,2021,13(5):592.）., and meanwhile, the traditional first-line and second-line antitubercular drugs have the problem of cross drug resistance and can also generate larger adverse reactions, so that the treatment effect is poor when facing patients with drug resistance or low immunity. Therefore, at the present day that the drug resistance problem of mycobacterium tuberculosis is more severe and the novel antitubercular drugs are relatively deficient, the research and development of more efficient antitubercular drugs and innovative therapies to overcome the treatment dilemma of drug-resistant tuberculosis has great significance （World Health Organization. Global Tuberculosis Report 2024[R]. Geneva: World Health Organization, 2024.）. NSC348884 is a small molecule reported by Qi et al in 2008, can up-regulate p53 and p21, induce apoptosis of cancer cells and enhance the killing effect of doxorubicin, and has shown broad-spectrum antiproliferative activity in a number of in vitro experiments. The study shows that NSC348884 can inhibit proliferation of cells in various cancer cell lines, including prostate cancer, colon cancer, breast cancer and lymphatic cancer （Qi W, Shakalya K, Stejskal A, et al. NSC348884, a nucleophosmin inhibitor disrupts oligomer formation and induces apoptosis in human cancer cells[J]. Oncogene, 2008, 27(30): 4210-4220.）., and the inhibition of mycobacterium tuberculosis has not been reported. Disclosure of Invention The present invention has been completed based on the finding that NSC348884 has an effect of inhibiting the activity of Mycobacterium tuberculosis. In a first aspect, the invention provides the use of NSC348884 in the preparation of a product for inhibiting Mycobacterium tuberculosis. Further, the Mycobacterium tuberculosis includes Mycobacterium tuberculosis standard strain, mycobacterium tuberculosis clinical isolate or Mycobacterium tuberculosis carried by patient infected with Mycobacterium tuberculosis. Further, the mycobacterium tuberculosis inhibiting product includes a medical product or a non-medical product. Further, the medical product refers to a drug or a pharmaceutical adjuvant, and the non-medical product refers to a bacteriostatic agent. Further, one or more pharmaceutically acceptable carriers or excipients are included in the product. Still further, the carrier material comprises one or more of a water-soluble carrier material, a poorly soluble carrier material, and/or an enteric carrier material. In a second aspect, the present invention provides the use of NSC348884 in the manufacture of a medicament for the prevention and/or treatment of a disease caused by a Mycobacterium tuberculosis infection, said NSC348884 acting by inhibiting the activity of Mycobacterium tuberculosis. Further, the Mycobacterium tuberculosis includes Mycobacterium tuberculosis standard strain, mycobacterium tuberculosis clinical isolate or Mycobacterium tuberculosis carried by patient infected with Mycobacterium tuberculosis. Further, one or more pharmaceutically acceptable ca