Thiol-independent DNA cleavage by a leinamycin degradation product

To understand the mechanism of action of a novel antitumor antibiotic leinamycin (1) which induces single-strand scission of DNA in the presence of thiol, the reaction of 1 with thiol in aqueous conditions was investigated. Two major degradation products were obtained from 1 in the presence of thiol. 2 was an inactive product, while 3 caused DNA cleavage in the absence of thiol. The DNA-cleaving activity of their synthetic derivatives indicates that the DNA alkylation and subsequent strand scission by leinamycin require the conversion of leinamycin to an electrophilic episulfonium species.