The Development of New DNA Alkylating Antitumour Agents Modeled on the Natural Product CC-1065

Abstract

Preliminary studies have revealed that the 4-hydroxyphenethyl halides possess the minimal structural requirements needed to mimic the DNA alkylation profile characteristic to seco-CPI subunits. Subsequent assessment of the 4-aminophenethyl halides showed that these adducts exhibit approximately four times the in vitro cytotoxicity demonstrated by their phenolic counterparts. The incorporation of these simpler compounds into more complex molecules containing non-covalent binding subunits was expected to increase both cytotoxicity and sequence selectivity. Biological assessment of the synthesized compounds established that the simplest compound, 4-aminophenethyl bromide, was a potent antitumor drug which exhibited selectivity for tumor cells over normal fibroblastic cells. This makes 4-aminophenethyl bromide an interesting candidate for further in vivo assessment.