On the antitumor activity of certain derivatives of sarcolysin (DL-n-di-(2-chlorethyl) aminophenylalanine)

Summary

Four modifications of sarcolysin were prepared. Two were substitutions in the carboxyl group: ethyl and isopropyl ethers of DL-sarcolysin; and two were substitutions in the amino group: DL-N-formylsarcolysin and DL-N-acetylsarcolysin. Animal tests were performed on rat sarcoma 45, a total of 229 rats being used to determine the LD₅₀ and also the antitumor effect.

The carboxyl group substitutions were very similar in effects to sarcolysin itself. The amino substituted compounds were both less toxic and less effective against tumors. However, while in N-formylsarcolysin the difference between the toxic and therapeutic doses is less than in sarcolysin, the lethal dose of the N-acetyl-sarcolysin is about 4 times greater than the dose for sarcolysin itself. Thus, the therapeutic dose of this last modification has twice the safety of the corresponding sarcolysin dosage.

This last result has aroused interest in replacing the amino group with longer alkylated chains. Studies with such compounds are now in progress.