Pyrimidine Antagonists

Abstract

In order for any pathological state to be treated successfully by chemotherapy, an exploitable biochemical difference must exist between the host and its unwelcome visitor. While this approach has been eminently successful in the case of bacterial, fungal, and, to some extent, parasitic infections, less impressive results, unfortunately, have been obtained with neoplastic disease. The reasons for this dichotomy become obvious when metabolic and structural differences between the host and the invading organisms are enumerated, differences that may be exploited with metabolic antagonists that are selectively toxic to the offending cells, but do little or no damage to the host. The rationale for this fact has been amply documented in the case of the microbial antibiotics, and has become the key to successful chemotherapy. Thus, the peptidoglycan component of the bacterial cell wall, a material completely foreign to animal cells, is impaired at specific steps in its synthesis by penicillin and bacitracin with little detriment to the host (Strominger, 1968–1969; Storm and Strominger, 1974). In a similar vein, the cell wall of fungi is damaged by the polyene antibiotics (Novak, 1971).