Berbamine derivative and application of salt thereof

Abstract

The invention provides an application of a type of berbamine derivatives and salts thereof in the preparation of drugs for the treatment of tumors, which is mainly applied in the preparation of the drugs for the prevention and treatment of nuclear transcription factor NF-kBp65 activity-related diseases and BCR/ABL transcription activity-related diseases. The drugs are combined and prepared by the compounds of the invention and one or more pharmaceutically acceptable excipients. The preparation forms comprise solid preparations, semi-solid preparations or liquid preparations. The type of berbamine derivatives and the salts thereof provided by the invention have broader and stronger anti-leukemia and anti-solid-tumor activity, the tumors proved to be sensitive are leukemia, multiple myeloma, liver cancer, osteosarcoma and breast cancer; the toxicity and the side effects are lighter. An in vitro cell culture system and animal experiments confirm that the berbamine derivatives and the salts thereof have no significant toxicity or side effects to the growth of normal human hematopoietic cells and experimental animals under the anti-tumor dosage, which are superior to the commonly used chemotherapy drugs.

Description

technical field [0001] The present invention relates to the application of compounds and derivatives thereof, and mainly relates to the application of berbamine derivatives and salts thereof. Background technique [0002] The BCR / ABL fusion gene is an oncogene formed by the fusion of the ABL gene on chromosome 9 and the BCR gene on chromosome 22 of hematopoietic cells, which is found in more than 95% of chronic myeloid leukemia and 20-30% of acute lymphoblastic leukemia [Lancet 2007;370:342-50]. A large amount of research data has confirmed that: the tyrosine protein kinase expressed by the BCR / ABL fusion gene is one of the main factors leading to the malignant proliferation of leukemia cells. According to this pathogenesis, Druker et al. found in 1996 that: tyrosine protein kinase inhibitor imatinib (imatinib) can effectively treat BCR / ABL fusion gene-positive leukemia, including chronic myeloid leukemia and acute lymphoblastic leukemia [N Engl J Med. 2001, 344: 1038-1042...

AI Technical Summary

Problems solved by technology

So far, there have been no reports or patents that other berbamine derivatives and their salts except 4ethoxybutyl berbamine can antagonize the transcription of BCR / ABL fusion gene and the activity of nuclear transcription factor NF-κB. 4 Berbamine derivatives other than ethoxybutyl berbamine and their salts are used in the preparation of hematological malignancies such as leukemia, multiple myeloma, lymphoma, and solid tumors such as liver cancer, lung cancer, breast cancer, and prostate cancer , Osteosarcoma and other drug application research and patent reports

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