Chapter 13. Antineoplastic Agents

Abstract

Publisher Summary A great deal of research continued to be stimulated by the clinical efficacy of compounds, such as cyclophosphamide, L-phenylalanine mustard (1-PAM), bis-chloroethyl nitrosourea, and close analogs as antineoplastic agents. With the development of chlororotocin and streptorotocin additional work has sought further decreases in the toxicity and advantages in activity profile. The absolute configuration of cyclophosphamide is obtained by x-ray diffraction and allows the determination of the absolute configuration at the phosphorus of all chiral metabolites of cyclophosphamide. The screening of compounds from fermentation and other natural sources continue to provide the greatest number of new antineoplastic agents. Two antibiotics structurally related to bleomycin, tallysomycin A and B are identified as having antitumor activity comparable to bleoniycin. Antitumor activity against a solid tumor in mice is studied for a new antitumor antibiotic, sporamycin. A group of fermentation-derived ansamycins, similar in structure to maytansine and active against a broad range of tumor systems, displayed strongest activity against P388 leukemia in mice at low daily doses. Activity against inurine P388 leukemia is also observed when treated with fatty acid containing 12-6 carbons, gycine, or β-alanine.