الفهرس | Only 14 pages are availabe for public view |
Abstract A very common story is that a basic scientist works for years and years to develop a new agent with a unique mechanism of action to treat tumor cells; but that new agent never makes it into clinical trials, or if it does, it almost always fails to make an impact on the disease. The naphthalimide DNA intercalating agents were designed to incorporate the essential structural components of several well-recognized antitumor moieties, including aristolochic acid, tilorone, CG-603, and cycloheximide into a single molecule. The naphthalimides inhibit both RNA and DNA synthesis, and the relegation step of topoisomerase II action. Early clinical evaluations of the mono-naphthalimides, amonafide and mitonafide, were performed in the 1980s. Naphthalimides form a famous class of intercalating agents that consists of a flat, generally π-deficient aromatic or heteroaromatic system, which binds to DNA by insertion between base pairs of the double helix. Many of them have not only shown high antitumor activities upon a variety of murine and human tumor cells but also capabilities of generating a multitude of reactive intermediates that resulted in DNA photocleavage. Various attempts made to modify the naphthalimide units to promote their DNA antitumor activity. Moreover, considerable interest has been focused on dithiocarbamates derivatives in the field of drug discovery because of their wide array of pharmacological activities, especially anticancer activities. |