Design, synthesis, and biological evaluation of a cephalosporin–monohydroguaiaretic acid prodrug activated by a monoclonal antibody–β-lactamase conjugate
| Autor: | Kak-Shan Shia, Shahram Hakimelahi, ‖ Hui-Ching Mei, Gholam Hossein Hakimelahi, Mostafa Rezaei-Tavirani, Mohammad N. Soltani, Manijeh Pasdar, Nai-Wen Mei, Ali Akbar Moosavi-Movahedi, Ali Akbar Saboury, Ali Khalafi-Nezhad |
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| Rok vydání: | 2002 |
| Předmět: |
Immunoconjugates
Antibodies Neoplasm medicine.drug_class Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Monoclonal antibody Biochemistry beta-Lactamases chemistry.chemical_compound Pancreatic cancer Drug Discovery Tumor Cells Cultured medicine Humans Masoprocol Prodrugs Molecular Biology Hydrolysis Organic Chemistry Drug Synergism Prodrug medicine.disease Fusion protein In vitro Cephalosporins Nordihydroguaiaretic acid chemistry Drug Design Cancer research Molecular Medicine Drug Screening Assays Antitumor Cell Division Conjugate K562 cells |
| Zdroj: | Bioorganic & Medicinal Chemistry. 10:2927-2932 |
| ISSN: | 0968-0896 |
| Popis: | A novel cephalosporin derivative of monohydroguaiaretic acid (cephem-M(3)N, 7) was synthesized and found to possess anticancer activity against human leukemia (K562), breast carcinoma (MCF7), human lung cancer (A549), human colon cancer (Colo205) and pancreatic cancer cells (Capan2 and MiaPaCa2). A tumor targeting fusion protein (dsFv3-beta-lactamase) was also used in conjunction with cephem-based M(3)N 7 and its potency toward K562, MCF7, A549, Colo205, Capan2, and MiaPaCa2 was found to approach that of the free M(3)N (4). In the presence of dsFv3-beta-lactamase, tumor cells were found to be much more susceptible to conjugate 7 than normal human embryonic lung (HEL) cells and normal fibroblasts (Hef522). These notions provide a new approach to the use of nordihydroguaiaretic acid (NDGA) and its derivatives for antitumor therapy. |
| Databáze: | OpenAIRE |
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