Peptides, amides, and esters of chlorethylamino derivatives of amino acids and of phenylalkancarboxylic acids: a new class of antitumor compounds.

The first stage of these studies consisted in the development of antitumor drugs of the type of alkylating metabolites 1952-55 (5, 6, 13). These are metabolites or other natural or biologically active compounds which are combined with a cytotoxic group (e.g., the chloroethylamino group). Sarcolysin and dopan are representative of drugs of this type. In the former, the essential amino acid, phenylalanine, acts as a metabolite carrier; and in the latter, uracil (or 4-methyl-uracil). Sarcolysin and dopan have dif ferent actions on the spectrum of animal and human tumors. Thus, dopan is effective in Hodgkin's disease and chronic myelogenous and lymphatic leukemia (8), and sarcolysin is ineffective in Hodgkin's disease but gives positive results in seminoma, reticulosarcoma, multiple myeloma, Ewing's bone tumor, primary cancer of the liver and ovaries (1, 15). These differences suggest a definite role of the "carrier" of the cyto