Interstrand cross-links (ICLs) are highly toxic DNA lesions that can block DNA transcription and replication. ICLs are the source of the cytotoxicity of many anti-tumor agents. Interest in the development of cancer therapies with improved selectivity and reduced host toxicity has been growing.1�2 One effective approach is to design prodrugs that can be activated under tumor-specific conditions, such as ROS-activated DNA cross-linking agents.3-5 Novel arylboronic ester derivatives capable of cross-linking DNA have been designed and synthesized. Their inducible DNA cross-linking ability and reaction mechanism were determined. Compound 1 which has a better leaving group (Br) can be selectively activated by hydrogen peroxide leading to hydroquinone derivative 1a that produces DNA cross-linking via quinine methides (QM) under physiological condition, while DNA ICLs were not observed for 2 upon hydrogen peroxide treatment. QM was not generated from hydroquinone derivative 2a which has a poor leaving group (N+Me3 Br�). However, 2 can be activated by UV-photolysis forming DNA ICLs via free radical mechanism. Figure 1. <img src='https://acs-archive-assets2.s3.amazonaws.com/239nm/uploads/12822_fig1_quadrelli__acs.jpg' alt='' />

Leaving group greatly affects the mechanism of DNA cross-linking formation induced by arylboronates

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.