Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates
Hybrid molecules combining photoactivated aryl acetylenes and a dicationic lysine moiety cause the most efficient double-strand (ds) DNA cleavage known to date for a small molecule. In order to test the connection between the alkylating ability and the DNA-damaging properties of these compounds, we...
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doaj-181b1193c91848c281986ac66152515b2021-02-02T03:26:46ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972011-06-017181382310.3762/bjoc.7.931860-5397-7-93Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugatesWang-Yong Yang0Samantha A. Marrone1Nalisha Minors2Diego A. R. Zorio3Igor V. Alabugin4Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390, USADepartment of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390, USADepartment of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390, USADepartment of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390, USADepartment of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390, USAHybrid molecules combining photoactivated aryl acetylenes and a dicationic lysine moiety cause the most efficient double-strand (ds) DNA cleavage known to date for a small molecule. In order to test the connection between the alkylating ability and the DNA-damaging properties of these compounds, we investigated the photoreactivity of three isomeric aryl–tetrafluoropyridinyl (TFP) alkynes with amide substituents in different positions (o-, m-, and p-) toward a model π-system. Reactions with 1,4-cyclohexadiene (1,4-CHD) were used to probe the alkylating properties of the triplet excited states in these three isomers whilst Stern–Volmer quenching experiments were used to investigate the kinetics of photoinduced electron transfer (PET). The three analogous isomeric lysine conjugates cleaved DNA with different efficiencies (34, 15, and 0% of ds DNA cleavage for p-, m-, and o-substituted lysine conjugates, respectively) consistent with the alkylating ability of the respective acetamides. The significant protecting effect of the hydroxyl radical and singlet oxygen scavengers to DNA cleavage was shown only with m-lysine conjugate. All three isomeric lysine conjugates inhibited human melanoma cell growth under photoactivation: The p-conjugate had the lowest CC50 (50% cell cytotoxicity) value of 1.49 × 10−7 M.https://doi.org/10.3762/bjoc.7.93cancer cell proliferation assayDNA alkylationlysine conjugatephotocycloadditionphoto-DNA cleavageplasmid relaxation assaytriplet excitation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wang-Yong Yang Samantha A. Marrone Nalisha Minors Diego A. R. Zorio Igor V. Alabugin |
spellingShingle |
Wang-Yong Yang Samantha A. Marrone Nalisha Minors Diego A. R. Zorio Igor V. Alabugin Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates Beilstein Journal of Organic Chemistry cancer cell proliferation assay DNA alkylation lysine conjugate photocycloaddition photo-DNA cleavage plasmid relaxation assay triplet excitation |
author_facet |
Wang-Yong Yang Samantha A. Marrone Nalisha Minors Diego A. R. Zorio Igor V. Alabugin |
author_sort |
Wang-Yong Yang |
title |
Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates |
title_short |
Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates |
title_full |
Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates |
title_fullStr |
Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates |
title_full_unstemmed |
Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates |
title_sort |
fine-tuning alkyne cycloadditions: insights into photochemistry responsible for the double-strand dna cleavage via structural perturbations in diaryl alkyne conjugates |
publisher |
Beilstein-Institut |
series |
Beilstein Journal of Organic Chemistry |
issn |
1860-5397 |
publishDate |
2011-06-01 |
description |
Hybrid molecules combining photoactivated aryl acetylenes and a dicationic lysine moiety cause the most efficient double-strand (ds) DNA cleavage known to date for a small molecule. In order to test the connection between the alkylating ability and the DNA-damaging properties of these compounds, we investigated the photoreactivity of three isomeric aryl–tetrafluoropyridinyl (TFP) alkynes with amide substituents in different positions (o-, m-, and p-) toward a model π-system. Reactions with 1,4-cyclohexadiene (1,4-CHD) were used to probe the alkylating properties of the triplet excited states in these three isomers whilst Stern–Volmer quenching experiments were used to investigate the kinetics of photoinduced electron transfer (PET). The three analogous isomeric lysine conjugates cleaved DNA with different efficiencies (34, 15, and 0% of ds DNA cleavage for p-, m-, and o-substituted lysine conjugates, respectively) consistent with the alkylating ability of the respective acetamides. The significant protecting effect of the hydroxyl radical and singlet oxygen scavengers to DNA cleavage was shown only with m-lysine conjugate. All three isomeric lysine conjugates inhibited human melanoma cell growth under photoactivation: The p-conjugate had the lowest CC50 (50% cell cytotoxicity) value of 1.49 × 10−7 M. |
topic |
cancer cell proliferation assay DNA alkylation lysine conjugate photocycloaddition photo-DNA cleavage plasmid relaxation assay triplet excitation |
url |
https://doi.org/10.3762/bjoc.7.93 |
work_keys_str_mv |
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