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

A novel cephalosporin derivative of monohydroguaiaretic acid (cephem-M3N, 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 M3N 7 and its potency toward K562, MCF7, A549, Colo205, Capan2, and MiaPaCa2 was found to approach that of the free M3N (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.