O-Benzoyl derivatives of meta-, orthoand para-pyridine aldoximes and amidoximes are novel efficient DNA photo-cleavage agents. In particular O-p-nitro-benzoyl derivatives 4, 8 and 15 were effective at concentrations as low as 1 μM. Both aldoximes and amidoximes were active under aerobic and anaerobic conditions, with a double-stranded to single-stranded DNA cleavage ratio of up to 1. These results give prospects for multiple applications, including phototherapeutic treatment of solid tumors.Med. Chem. Commun. This journal isThessaloniki, 54124, Thessaloniki, Greece † Electronic supplementary information (ESI) available: 1 H and 13 C-NMR spectra of all compounds, photochemistry and pH experiments, and UV spectra are available. See