A Synthetic Azinomycin Analogue with Demonstrated DNA Cross-Linking Activity: Insights into the Mechanism of Action of this Class of Antitumor Agent

An efficient synthesis of simplified azinomycin A and B analogues 1 and 2 (see picture) is described, and it is demonstrated that only 1, bearing both the epoxide and aziridine, induces interstrand cross-links in double-stranded DNA. Remarkably, a compound structurally related to 1 but devoid of the aziridine ring exhibited comparable in vitro cytotoxicity, suggesting that in cells the epoxide is largely responsible for the antitumor activity of these agents.