title: Alkyl and aryl sulfonyl p-pyridine ethanone oximes are efficient DNA photo-cleavage agents.
abstract: Sulfonyloxyl radicals, readily generated upon UV irradiation of p-pyridine sulfonyl ethanone oxime derivatives, effectively cleave DNA, in a pH independent manner, and under either aerobic or anaerobic conditions. p-Pyridine sulfonyl ethanone oxime derivatives were synthesized from the reaction of p-pyridine ethanone oxime with the corresponding sulfonyl chlorides in good to excellent yields. All compounds, at a concentration of 100μM, were irradiated at 312nm for 15min, after incubation with supercoiled circular pBluescript KS II DNA and resulted in extended single- and double- strand cleavages. The cleavage ability was found to be concentration dependent, with some derivatives exhibiting activity even at nanomolar levels. Besides that, p-pyridine sulfonyl ethanone oxime derivatives showed good affinity to DNA, as it was observed with UV interaction and viscosity experiments with CT DNA and competitive studies with ethidium bromide. The compounds interact to CT DNA probably by non-classical intercalation (i.e. groove-binding) and at a second step they may intercalate within the DNA base pairs. The fluorescence emission spectra of pre-treated EB-DNA exhibited a significant or moderate quenching. Comparing with the known aryl carbonyloxyl radicals the sulfonyloxyl ones are more powerful, with both aryl and alkyl sulfonyl substituted derivatives to exhibit DNA photo-cleaving ability, in significantly lower concentrations. These properties may serve in the discovery of new leads for "on demand" biotechnological and medical applications.
authors.affiliation: Laboratory of Organic, Bioorganic and Natural Product Chemistry, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, 68100 Alexandroupolis, Greece.
authors.forename: Nicolaos-Panagiotis
authors.initials: NP
authors.lastname: Andreou
authors.affiliation: Laboratory of Organic, Bioorganic and Natural Product Chemistry, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, 68100 Alexandroupolis, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Dafnopoulos
authors.affiliation: Laboratory of Organic, Bioorganic and Natural Product Chemistry, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, 68100 Alexandroupolis, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Tortopidis
authors.affiliation: Laboratory of Organic Chemistry, Chemistry Department, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
authors.forename: Alexandros E
authors.initials: AE
authors.lastname: Koumbis
authors.affiliation: Laboratory of Cellular Biology and Cell Cycle, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, 68100 Alexandroupolis, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Koffa
authors.affiliation: Laboratory of Inorganic Chemistry, Chemistry Department, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Psomas
authors.affiliation: Laboratory of Organic, Bioorganic and Natural Product Chemistry, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, 68100 Alexandroupolis, Greece. Electronic address: kfylakta@mbg.duth.gr.
authors.forename: Konstantina C
authors.initials: KC
authors.lastname: Fylaktakidou
mesh_terms: D004247:DNA / Q000737:chemistry*; D006868:Hydrolysis; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology*; D010777:Photochemistry; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D010091:Oximes; D011725:Pyridines; D004247:DNA
keywords: DNA binding; DNA photo-cleavage; Photo-cleavage agents; Sulfonyl ketoximes; Sulfonyloxyl radicals