O-Benzoyl pyridine aldoxime and amidoxime derivatives: novel efficient DNA photo-cleavage agents

Abstract

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

Alkyl and aryl sulfonyl p-pyridine ethanone oximes are efficient DNA photo-cleavage agents

“…1 show that most of the aryl SKs are in general considerably reactive. The most important observation is that alkyl SRs are also effective, and, comparing to the aryl ones, they are similarly efficient at the given concentration, contrary to what was observed for the carbonyl analogues [7,8]. As for the aromatic ones, a SAR study revealed that lack of substitution on the aromatic ring (6) results in reduced activity.…”

“…1(B)]. Moreover, compared to the p-pyridine p-nitrobenzoyl oxime and amidoxime derivatives, the sulfonyl ones were found to exhibit a superior effect on cleavage: approximately 10-fold lower concentrations were sufficient to lead to the same activity, along with similar ds/ss ratio cleavage (the effective concentration was 100 μM and 1000 μM, respectively) [7]. This is in accordance with previous literature kinetic results where SRs are reported to be more reactive compared to CRs [26].…”

“…Among DNA cleaving agents, those causing oxidative cleavage upon UV light activation are called "photo-cleavers" [4]. OAcyl oximes represent one such class of compounds [5][6][7], which yield photo-generated carbonyloxyl radicals (CRs) capable of causing oxidative DNA damage. However, their use is so far mainly limited to aryl conjugates, since the alkyl ones suffer rapid decarboxylation and produce less drastic radicals [8].…”

“…In continuation of our interest in the chemistry and biology of oximes [7,[14][15][16][17], we have decided to investigate the photo-activating behavior of SKs towards plasmid DNA. p-Pyridine ethanone oxime was selected as the model carrier scaffold of the sulfonyl moiety in order to facilitate comparison of the obtained results with the ones previously reported for the p-pyridine oxime and amidoxime ester conjugates [7].…”

“…p-Pyridine ethanone oxime was selected as the model carrier scaffold of the sulfonyl moiety in order to facilitate comparison of the obtained results with the ones previously reported for the p-pyridine oxime and amidoxime ester conjugates [7]. Additionally, after evaluating the derivative which exhibits the best cleaving activity, the p-nitro-phenyl ester conjugate of p-pyridine ethanone oxime was also synthesized, allowing, thus, the direct reactivity comparison between sulfonyloxyl and carbonyloxyl radicals.…”