Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies
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, amidoxim...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2016-06-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1420-3049/21/7/864 |
| _version_ | 1818904039285325824 |
|---|---|
| author | Milena Pasolli Konstantinos Dafnopoulos Nicolaos-Panagiotis Andreou Panagiotis S. Gritzapis Maria Koffa Alexandros E. Koumbis George Psomas Konstantina C. Fylaktakidou |
| author_facet | Milena Pasolli Konstantinos Dafnopoulos Nicolaos-Panagiotis Andreou Panagiotis S. Gritzapis Maria Koffa Alexandros E. Koumbis George Psomas Konstantina C. Fylaktakidou |
| author_sort | Milena Pasolli |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T21:01:06Z |
| format | Article |
| id | doaj.art-dcafb058c41648f1880518244408a347 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-19T21:01:06Z |
| publishDate | 2016-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-dcafb058c41648f1880518244408a3472022-12-21T20:05:49ZengMDPI AGMolecules1420-30492016-06-0121786410.3390/molecules21070864molecules21070864Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding StudiesMilena Pasolli0Konstantinos Dafnopoulos1Nicolaos-Panagiotis Andreou2Panagiotis S. Gritzapis3Maria Koffa4Alexandros E. Koumbis5George Psomas6Konstantina C. Fylaktakidou7Laboratory of Organic, Bioorganic and Natural Product Chemistry, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, GR-68100 Alexandroupolis, GreeceLaboratory of Organic, Bioorganic and Natural Product Chemistry, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, GR-68100 Alexandroupolis, GreeceLaboratory of Organic, Bioorganic and Natural Product Chemistry, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, GR-68100 Alexandroupolis, GreeceLaboratory of Organic, Bioorganic and Natural Product Chemistry, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, GR-68100 Alexandroupolis, GreeceLaboratory of Cellular Biology and Cell Cycle, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, GR-68100 Alexandroupolis, GreeceLaboratory of Organic Chemistry, Chemistry Department, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, GreeceLaboratory of Inorganic Chemistry, Chemistry Department, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, GreeceLaboratory of Organic, Bioorganic and Natural Product Chemistry, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, GR-68100 Alexandroupolis, GreeceCompared 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.http://www.mdpi.com/1420-3049/21/7/864photo-cleavageDNA photo-cleaversDNA bindingoxime estersamidoximealdoximeketoxime |
| spellingShingle | Milena Pasolli Konstantinos Dafnopoulos Nicolaos-Panagiotis Andreou Panagiotis S. Gritzapis Maria Koffa Alexandros E. Koumbis George Psomas Konstantina C. Fylaktakidou Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies Molecules photo-cleavage DNA photo-cleavers DNA binding oxime esters amidoxime aldoxime ketoxime |
| title | Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies |
| title_full | Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies |
| title_fullStr | Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies |
| title_full_unstemmed | Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies |
| title_short | Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies |
| title_sort | pyridine and p nitrophenyl oxime esters with possible photochemotherapeutic activity synthesis dna photocleavage and dna binding studies |
| topic | photo-cleavage DNA photo-cleavers DNA binding oxime esters amidoxime aldoxime ketoxime |
| url | http://www.mdpi.com/1420-3049/21/7/864 |
| work_keys_str_mv | AT milenapasolli pyridineandpnitrophenyloximeesterswithpossiblephotochemotherapeuticactivitysynthesisdnaphotocleavageanddnabindingstudies AT konstantinosdafnopoulos pyridineandpnitrophenyloximeesterswithpossiblephotochemotherapeuticactivitysynthesisdnaphotocleavageanddnabindingstudies AT nicolaospanagiotisandreou pyridineandpnitrophenyloximeesterswithpossiblephotochemotherapeuticactivitysynthesisdnaphotocleavageanddnabindingstudies AT panagiotissgritzapis pyridineandpnitrophenyloximeesterswithpossiblephotochemotherapeuticactivitysynthesisdnaphotocleavageanddnabindingstudies AT mariakoffa pyridineandpnitrophenyloximeesterswithpossiblephotochemotherapeuticactivitysynthesisdnaphotocleavageanddnabindingstudies AT alexandrosekoumbis pyridineandpnitrophenyloximeesterswithpossiblephotochemotherapeuticactivitysynthesisdnaphotocleavageanddnabindingstudies AT georgepsomas pyridineandpnitrophenyloximeesterswithpossiblephotochemotherapeuticactivitysynthesisdnaphotocleavageanddnabindingstudies AT konstantinacfylaktakidou pyridineandpnitrophenyloximeesterswithpossiblephotochemotherapeuticactivitysynthesisdnaphotocleavageanddnabindingstudies |