Thiol-dependent DNA cleavage by 3H-1,2-benzodithiol-3-one 1,1-dioxide

Hydrodisulfides (RSSH) have previously been implicated as key intermediates in thiol-triggered oxidative DNA damage by the antitumor agent leinamycin. In an effort to better understand DNA damage by RSSH and to expand on the number and type of chemical systems that produce this reactive intermediate, the ability of 3H-1,2-benzodithiol-3-one 1,1-dioxide (11) to serve as a thiol-dependent DNA cleaving agent has been investigated. The findings reported here indicate that reaction of 11 with thiols results in release of RSSH and subsequent oxidative DNA strand cleavage. Scheme 2. Proposed reaction of thiols with 3H-1,2-benzodithiol-3-one 1,1-dioxide (11). Scheme 3. Products resulting from attack of thiol on 3H-1,2-benzodithiol-3-one 1,1-dioxide (11).