Design, synthesis, and biological evaluation of a cephalosporin–monohydroguaiaretic acid prodrug activated by a monoclonal antibody–β-lactamase conjugate

A novel cephalosporin derivative of monohydroguaiaretic acid (cephem-M 3N, 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 t...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2002-09, Vol.10 (9), p.2927-2932
Main Authors: Hakimelahi, Gholam Hossein, Shia, Kak-Shan, Pasdar, Manijeh, Hakimelahi, Shahram, Khalafi-Nezhad, Ali, Soltani, Mohammad N, Mei, Nai-Wen, Mei, Hui-Ching, Saboury, Ali A, Rezaei-Tavirani, Mostafa, Moosavi-Movahedi, Ali A
Format: Article
Language:English
Subjects:
Antibodies, Neoplasm
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - metabolism
Antineoplastic Agents - pharmacology
beta-Lactamases - immunology
beta-Lactamases - metabolism
beta-Lactamases - pharmacology
Biological and medical sciences
Cell Division - drug effects
Cephalosporins
Drug Design
Drug Screening Assays, Antitumor
Drug Synergism
General aspects
Humans
Hydrolysis - drug effects
Immunoconjugates - metabolism
Immunoconjugates - pharmacology
Masoprocol
Medical sciences
Pharmacology. Drug treatments
Prodrugs - chemical synthesis
Prodrugs - metabolism
Prodrugs - pharmacology
Tumor Cells, Cultured
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Summary:A novel cephalosporin derivative of monohydroguaiaretic acid (cephem-M 3N, 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–β-lactamase) was also used in conjunction with cephem-based M 3N 7 and its potency toward K562, MCF7, A549, Colo205, Capan2, and MiaPaCa2 was found to approach that of the free M 3N ( 4). In the presence of dsFv3–β-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. Graphic
ISSN:0968-0896
1464-3391
DOI:10.1016/S0968-0896(02)00140-2