Oxime Esters of 2,6-Diazaanthracene-9,10-dione and 4,5-Diazafluoren-9-one as Photo-induced DNA-Cleaving Agents

Chou, Shang‐Shing P.; Juan, Jui-Chi; Tsay, Shwu‐Chen; Huang, Kuei Pin; Hwu, Jih Ru

doi:10.3390/molecules17033370

Cited by 13 publications

(6 citation statements)

References 27 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nitro substituted compounds have been studied for their ability to cleave DNA, thus, the p -nitrophenyl moiety may also contribute to the observed DNA photocleavage [51,52,53,54]. In the case of the oxime esters it was evidenced, via photo-chemical experiments, that the aroyloxyl or sulfonyloxyl radicals are the active intermediates for the carboxylic [24,25,26,27,28,29,30,31,32,33] or the sulfonic esters [34,35], respectively. Mechanistically, these radicals derive upon the homolysis of the N-O bond of the oxime derivatives, as depicted in Scheme 1.…”

Section: Resultsmentioning

confidence: 99%

“…They, additionally, participate as parent compounds in multiple transformations leading to biologically interesting derivatives [18,19,20,21,22,23]. Oxime carboxylates (Figure 1, general structures Ib , IIb and IIIb ) have the ability to act as metal free DNA photocleavers, with aroyl conjugates shown to be the most active ones [24,25,26,27,28,29,30]. In this case, homolysis of the weak N-O bond of the oximes generates active aroyloxyl radicals (ArCOO · ) able to attack DNA.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies

et al. 2016

View full text Add to dashboard Cite

Compared to standard treatments for various diseases, photochemotherapy and photo-dynamic therapy are less invasive approaches, in which DNA photocleavers represent promising tools for novel "on demand" chemotherapeutics. A series of p-nitrobenzoyl and p-pyridoyl ester conjugated aldoximes, amidoximes and ethanone oximes were subjected to UV irradiation at 312 nm with supercoiled circular plasmid DNA. The compounds which possessed appropriate properties were additionally subjected to UVA irradiation at 365 nm. The ability of most of the compounds to photocleave DNA was high at 312 nm, whereas higher concentrations were required at 365 nm as a result of their lower UV absorption. The affinity of selected compounds to calf-thymus (CT) DNA was studied by UV spectroscopy, viscosity experiments and competitive studies with ethidium bromide (EB) revealing that all compounds interacted with CT DNA. The fluorescence emission spectra of the pre-treated EB-DNA exhibited a moderate to significant quenching in the presence of the compounds indicating the binding of the compounds to CT DNA via intercalation as concluded also by DNA-viscosity experiments. For the oxime esters the DNA photocleavage and affinity studies aimed to clarify the role of the oxime nature (aldoxime, ketoxime, amidoxime) and the role of the pyridine and p-nitrophenyl moieties both as oxime substituents and ester conjugates.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies

et al. 2016

View full text Add to dashboard Cite

show abstract

“…10 O-Acyl aldoximes, ketoximes as well as O-acyl amid-oximes (I, Fig. 1) represent typical classes of such compounds, [11][12][13][14][15][16][17] which yield photo-generated carbonyloxyl radicals (CRs) capable of causing oxidative DNA damage. However, their use is mainly limited to aryl conjugates, since the alkyl ones suffer rapid decarboxylation producing less drastic radicals.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of O-alkyl and aryl sulfonyl aromatic and heteroaromatic amidoximes as novel potent DNA photo-cleavers

Papastergiou

Perontsis

Gritzapis

et al. 2016

Photochem Photobiol Sci

View full text Add to dashboard Cite

Several stable O-alkyl and aryl sulfonyl conjugated p-nitro-Ph and o-, m-, p-pyridine N'-hydroxy imidamides, were subjected to UV irradiation at 312 nm with supercoiled circular plasmid DNA pBluescript KS II. The generated amidinyl and sulfonyloxyl radicals led to effective DNA photo-cleavage. Both alkyl and aryl sulfonyl derivatives were active and the order p-pyridine > p-nitro-Ph > o-pyridine > m-pyridine was schematized for the N'-hydroxy imidamides moiety. Calf thymus-DNA affinity studies which comprised UV interactions, viscosity experiments and competitive studies with ethidium bromide showed good to excellent affinity of the compounds. These properties revealed sulfonyl amidoximes as novel effective DNA-photo-cleavers and may serve in the discovery of new leads for "on demand" biotechnological and medical applications.

show abstract

“…O-Acyl amidoximes, ketoximes and aldoximes (I, II and III, respectively, Figure 1) are also recognized as DNA "photocleavage" agents owing their action to the homolysis of their vulnerable N-O bond, at 312 nm [9,[39][40][41][42][43] or 365 nm [44,45] yielding photogenerated carbonyloxyl radicals (CRs), which are able to cause oxidative DNA damage. We have recently reported the DNA photocleavage from sulfonylamidoximes and ethanone oximes (IV and V, Figure 1), which were found to attack DNA via sulfonyloxyl radicals (SRs) [10,11].…”

Section: Introductionmentioning

confidence: 99%

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

Gritzapis

Varras

Andreou

et al. 2020

Beilstein J. Org. Chem.

View full text Add to dashboard Cite

A number of p-pyridinyl oxime carbamate derivatives were prepared upon the reaction of the corresponding oximes with isocyanates. These novel compounds reacted photochemically in the presence of supercoiled plasmid DNA. Structure–activity relationship (SAR) studies revealed that the substituent on the imine group was not affecting the extend of the DNA damage, whereas the substituent of the carbamate group was critical, with the halogenated derivatives to be able to cause extensive single and double stranded DNA cleavages, acting as “synthetic nucleases”, independently of oxygen and pH. Calf thymus–DNA affinity studies showed a good-to-excellent affinity of selected both active and non-active derivatives. Preliminary theoretical studies were performed, in an effort to explain the reasons why some derivatives cause photocleavage and some others not, which were experimentally verified using triplet state activators and quenchers. These theoretical studies seem to allow the prediction of the activity of derivatives able to pass intersystem crossing to their triplet energy state and thus create radicals able to damage DNA. With this study, it is shown that oxime carbamate derivatives have the potential to act as novel effective photobase generating DNA-photocleavers, and are proposed as new leads for “on demand” biotechnological applications in drug discovery and medicine.

show abstract

Oxime Esters of 2,6-Diazaanthracene-9,10-dione and 4,5-Diazafluoren-9-one as Photo-induced DNA-Cleaving Agents

Cited by 13 publications

References 27 publications

Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies

Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies

Evaluation of O-alkyl and aryl sulfonyl aromatic and heteroaromatic amidoximes as novel potent DNA photo-cleavers

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

Contact Info

Product

Resources

About